Wako Pure Chemical Industries, Inc.

Shimadzu Corporation

Shinji Satomura

Kenji Nakamura

Hideo Katoh

Tomohisa Kawabata

Tokuji Ikenaka

Kaoru Omichi

Henry Garrett Wada

Nobuhiro Hanafusa

Koji Tanimizu

Masayoshi Hayashi

Nobuko Imajo

Yukari Yamagata

Hideyoshi Arashima

Tetsushi Okuyama

Yuko Nagamine

Akira Hasegawa

Makoto Kiso

Shuji Matuura

Kazunari Hirayasu

Yoshinobu Miyashita

Taizo Hara

Ritsu Yamamoto

An object of the present invention is to provide a method for forming a complex between an analyte or an analog thereof, and a substance formable the complex with said analyte or said analog thereof (the complex forming substance), in a short time and in high reaction efficiency, and a method for separating a complex formed, and a complex forming substance not involved in formation of said complex or an analog not involved in formation of said complex rapidly, simply and in high accuracy, along with a method for measuring an analyte in a sample in high sensitivity.

Complex formation method and separation method

The present invention relates to a structure (a solution introducing structure) for introducing a plurality of solutions (a sample and/or a reagent solution) in highly accurate volume, in high amount and simply, into a channel, in particular a channel of a micro fluidic device, a micro fluidic device having said structure, a method for introducing a solution using said device, a method for separation of a substance, and a method for separating a complex between an analyte or analogue thereof, and a substance binding to said analyte or analogue thereof (hereinafter may be abbreviated as a complex forming substance or CFS) which is obtained by reacting a plurality of solutions introduced by these, and said CFS or analogue not involved in formation of said complex, rapidly, simply and in high accuracy, along with a method for measuring an analyte or an analogue thereof in a sample in high sensitivity.

Structure for introducing a plurality of solutions, micro fluidic device having said structure and method for introducing solution

The invention relates to a method for separating a target for measurement utilizing electrophoresis, particularly capillary electrophoresis efficiently in high sensitivity and in a short period of time. It also relates to a method for measuring said target separated by said method for separation. The invention provides a method for separating a target for measurement and a method for measuring said target separated by said method for separation, characterized by using a substance to which is bound a nucleic acid chain labeled by a marker and which has an affinity for said target for measurement.

Electrophoresis

The present invention relates to a solution introducing structure for introducing a plurality of solutions (a sample and/or a reagent solution) in highly accurate volume, in high amount and simply, into a channel () of a micro fluidic device, said channel () comprising not less than three side channels () for drain and not less than two side channels () for introducing a sample or a reagent solution.

A living body component in a sample derived from a living body can be rapidly and accurately measured by reacting the sample with a reagent comprising a combined product of an affinity substance and a polypeptide having at least three acid residues derived from a strong acid, separating the resulting complex by a method applying negative change such as using an anion-exchanger, and determining the amount of the analyte to be measured, on the basis of the amount of the complex or free combined product.

Polypeptide and process for measuring living body components using the same

An increased risk of a fetal chromosomal abnormality, for example, fetal Down syndrome can be detected by separating or discriminating &agr;-fetoproteins present in the body fluid of a pregnant woman, and measuring the proportion of one or more of the &agr;-fetoproteins which have a specific sugar chain structure, relative to the total &agr;-fetoproteins.

Process for detecting increased risk of fetal chromosomal abnormality

The object of the present invention is to provide a method for separating components in a liquid specimen and an apparatus used in said method, by which it is possible to avoid carryover even when the specimen injector is not washed using washing solution and also to avoid the increase of inner pressure in column of the separation device or ineffective separating operation even when many liquid specimens are separated by many times using the same separation device. In the present invention, the liquid specimen is introduced into the separation device from a direction opposite to eluting direction of the separation device which retains an adsorbent, and by separating and eluting the specimen from eluting outlet together with the eluant, trace quantity of insoluble substances and the specimen remained on the specimen introducing passage can be removed by elution procedure. As a result, it is possible to avoid carryover, to prevent the increase of inner pressure in the column of the separation device and to prevent ineffective separating operation caused by clogging of the column.

Method for separating components in liquid specimen and apparatus used

Two or more analytes having the same action, or having different actions in spite of their similar structures, or two or more analytes having the same action and the same detectable chemical characteristics, in samples derived from living bodies, etc., can be measured rapidly and easily by forming one or more complexes with one or more affinity substances, separating the complexes by using high pressure liquid chromatography, followed by measurement of the amount of an affinity substance or one of the analytes.

Process for separating and measuring trace components

Trace components in samples can be measured rapidly with high precision by applying interaction between an analyte to be measured and an affinity substance and using a membrane having specific separating capability.

Process for rapid measurement of trace components

The degree of a structure change of the sugar chain of a glycoprotein caused by a disease can be measured with high precision rapidly by separating and measuring two or more forms of glycoproteins which are different in sugar chain structure but have substantially the same protein structure, by using a combination of a lectin capable of recognizing the specific sugar chain structure of at least one of these glycoprotein analytes to be measured, and a first antibody which has a property of binding to all the glycoprotein analytes but is kept from binding to glycoprotein analyte(s) having the lectin attached thereto; and separating and measuring glycoprotein analyte(s) having the first antibody attached thereto and glycoprotein analyte(s) having no first antibody attached thereto, by utilizing differences in properties between the former glycoprotein analyte(s) and the latter glycoprotein analyte(s).

Process for separating and measuring glycoprotein

This invention is intended to provide a process by which a complex formed by the interaction between one or more analytes to be measured and affinity substance can be more effectively separated from substances existing together therewith which tend to affect the detection of the complex, for example, free affinity substance, by using high pressure liquid chromatography (HPLC); and a process for measuring a trace component by utilizing said separating process. This invention is characterized in that a substance which has been modified with a substance capable of changing properties of the complex (a separation-improving substance) and has affinity for the complex is attached to the complex. Because of this characteristic, the invention is effective in that the position of elution of said complex in the HPLC can be freely controlled. Furthermore, it is markedly effective in that the process for measuring a trace component by utilizing the separating process of this invention makes it possible to carry out the measurement with higher precision as compared with conventional measuring processes using HPLC.

Process for separating complex

The amount of an analyte in a sample derived from a living sample is measured by reacting the analyte with an excess of a substance having affinity for the analyte, followed by separation of complex by high pressure liquid chromatography and measurement using a linear calibration curve representing the peak area values associated with known concentrations of analyte.

Process for measuring analyte in sample

.alpha.-Amylase activity can be determined rapidly and precisely by using as a substrate a modified oligo-saccharide wherein a benzylozymethyl group or a halo-methyl group is bonded to the C.sub.6 position of non-reducing-end glucose residue and the reducing-end glucose residue is bonded to a group which exhibits an optically measurable change upon cleavage. Processes for producing such a compound are also disclosed.

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Osaka, Japan

Shinji Satomura