Konica Minolta, Inc.

Tohoku University

Konica Minolta Medical and Graphic, Inc.

Hideki Gouda

Yasushi Nakano

Kohsuke Gonda

Noriaki Ohuchi

Kensaku Takanashi

Mika Watanabe

Hisatake Okada

Hideki Hoshino

Masaru Takahashi

Takeshi Isoda

Motohiro Takeda

Takuji Aimiya

Keizou Takano

Yasuhiro Watanabe

Yuichi Ozaki

Yuka Yoshihara

Fuminori Okada

Takashi Kamei

Masakazu Toi

Makoto Hikage

Minoru Miyashita

Hiroshi Tada

Norikazu Masuda

Keizu Takano

Hidecki Hoshino

It is an object of the present invention to provide a tissue staining method that makes it possible to observe both information on the morphology of a tissue and information on a biological substance such as an antigen molecule to be detected on a single section and in a single view field. The present invention provides a tissue staining method, including carrying out (A) a HE (hematoxylin-eosin) staining, and (B) a histochemical staining, serially on a single tissue section, wherein the histochemical staining is defined as a histochemical technique for detecting a biological substance to be detected in a tissue in a visible manner by use of a binding reaction between the biological substance to be detected and a probe biological substance capable of binding specifically to the biological substance to be detected.

Tissue staining method

The present invention relates to a test support method which is a means for predicting whether or not pathological complete response (pCR) will be attained when a preoperative chemotherapy with an anticancer drug is performed, the method using a sample (breast cancer tissue section) collected from a breast cancer patient to be subjected to the preoperative chemotherapy. The test support method includes: [1] the step of acquiring a fluorescence image of a breast cancer tissue section, which fluorescence image shows bright spots of fluorescent nanoparticles labeling one or more kinds of breast cancer-related proteins; [2] the step of acquiring at least one index relating to the expression level(s) of the breast cancer-related protein(s) on the basis of the bright spots of the fluorescence image; and [3] the step of acquiring information for predicting pCR by performing an analysis using the above-described at least one index.

Test support method for supporting prediction of pathological complete response (pCR) using fluorescent nanoparticles

For fluorescent nanoparticles having a zeta potential of &#x2212;10 mV to &#x2212;60 mV at pH 7.0 or a zeta potential of 0 mV to &#x2212;10 mV in a buffer of pH 6.0 to 8.0, an appropriate electrical repulsive force can be generated between biomolecules that are generally negatively charged and the fluorescent nanoparticles. As a result, non-specific binding between the fluorescent nanoparticles and the biomolecules is suppressed and the fluorescent nanoparticles are specifically bound to a biomolecule to be stained through interaction stronger than the electrical repulsive force, so that the visibility of the specific biomolecule to be stained can be improved. Further, since an appropriate electrical repulsive force is also generated between the fluorescent nanoparticles themselves, aggregation of the fluorescent nanoparticles can be inhibited and the dispersibility in a staining solution can thereby be maintained.

Fluorescent nanoparticles for biomolecular staining and manufacturing method for same

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.

Tissue staining method with staining agent containing particle holding plural phosphors

An analysis device for an objective biological substance includes a generator, a divider, an analyzer, and a calculator. The generator generates a microscopic image of a tissue sample after staining. The divider divides the microscopic image into at least one section having a prescribed size. The analyzer analyzes a staining condition of the microscopic image for each section. The calculator calculates a prescribed statistic based on an analysis result by the analyzer.

Objective biological substance analysis device, analysis system, analysis method, and recording medium storing computer readable analysis program

Fluorescent marker for tissue staining containing phosphor-containing nanoparticle and method using same

Provided are: a phosphor-integrated nanoparticle labeling agent which is capable of yielding a sufficient signal intensity even when its final concentration in an immunofluorescent staining reaction system is low (e.g., 0.02 nM) and enables to obtain an immunofluorescently stained image with reduced noise by inhibiting non-specific adsorption of a probe biological substance and a label to substances other than a detection subject; and an immunostaining method using the same. The phosphor-integrated nanoparticle labeling agent is a set which includes: a probe biological substance, which is linked to a first binding group substance A via a first hydrophilic polymer-derived spacerhaving a length of 30 &#x212b; to 1,000 &#x212b; and specifically binds to a biomolecule; and a phosphor-integrated nanoparticle, which has a second binding group substance B capable of specifically binding to the first binding group substance A.

Integrated phosphor nanoparticle marking agent, and fluorescent immunostaining employing same

The present invention provides a staining method in which the fluorescent staining properties in a fluorescently-immunostained specimen are not reduced even when an oil-based mounting medium is used. The present invention also provides a method of preventing deterioration of a fluorescent label caused by irradiation with excitation light and improving the light resistance in a fluorescently-immunostained specimen obtained by the staining method. The biological substance detection method according to the present invention is a biological substance detection method for specifically detecting a biological substance from a pathological specimen, which includes the steps of: immunostaining the specimen with a fluorescent label; immobilizing the thus stained specimen; and mounting the thus immobilized specimen using a mounting medium including an organic solvent not freely miscible with water. In the biological substance detection method, the above-described mounting medium further includes a discoloration inhibitor.

Method for detecting biological material

A biological substance quantitation method includes the following. A fluorescent image is input, which represents an expression of a specific biological substance in a sample stained with a fluorescent substance by a florescent bright spot. A quantitative evaluation value of the florescent bright spot is calculated. A standard fluorescent image of a standard sample stained under a same condition as the sample and representing an expression of the biological substance in a standard sample, is input under a same condition as the fluorescent image. A quantitative evaluation value in the standard fluorescent image is calculated under a same condition as the fluorescent image. Based on a correlation between an expression amount of the biological substance in a standard sample measured in advance and the evaluation value in the standard fluorescent image, the evaluation value in the fluorescent image is converted to an expression amount of the biological substance in the sample.

Biological substance quantitation method, pathological diagnosis support system and recording medium storing computer readable program

A biological substance quantitation method includes the following. A fluorescent image is input, which represents an expression of a specific biological substance in a sample stained with a fluorescent substance by a fluorescent bright spot. A quantitative evaluation value of the fluorescent bright spot is calculated. A standard fluorescent image of a standard sample stained under a same condition as the sample and representing an expression of the biological substance in a standard sample, is input under a same condition as the fluorescent image. A quantitative evaluation value in the standard fluorescent image is calculated under a same condition as the fluorescent image. Based on a correlation between an expression amount of the biological substance in a standard sample measured in advance and the evaluation value in the standard fluorescent image, the evaluation value in the fluorescent image is converted to an expression amount of the biological substance in the sample.

An object of the present invention is to provide: a staining agent for tissue staining which has an improved fluorescence signal evaluation accuracy; and a tissue staining kit comprising the staining agent. The staining agent for tissue staining contains, as a staining component, dye-resin particles comprising thermosetting resin particles and a fluorescent dye immobilized on the resin particles, wherein the resin particles contains a substituent having an electric charge opposite to that of the fluorescent dye and forms an ionic bond or a covalent bond with the fluorescent dye, and the dye-resin particles have a particle size variation coefficient of 15% or less.

Staining agent for staining tissue, production method for staining agent for staining tissue and tissue staining kit including staining agent for staining tissue

Provided is a method for staining a tissue enabling highly precise staining, by which the expression amount and/or the location of a biological substance in a tissue sample can be detected with a high quantitativity together with detailed information that can be obtained by bright field observation. The tissue staining method of the present invention is a method for staining a tissue, in which both staining that allows bright field observation and fluorescence staining are carried out for the same specific biological substance.

Growing community of inventors

Tokyo, Japan

Hideki Gouda