Labeled probe bound object, method for producing the same and method for using the same

• US 20070092897A1
• Filed: 08/07/2006
• Published: 04/26/2007
• Est. Priority Date: 08/09/2005
• Status: Active Grant

• Current Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Original Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Inventors: Okamoto, Tadashi
• Granted Patent: US 7,642,086 B2
• Time in Patent Office: Days
• US Class Current: 435/6.11
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 2563/137 Metal/ion, e.g. metal label
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2563/185 Nucleic acid dedicated to use as a hidden marker/bar code, e.g. inclusion of nucleic acids to mark art objects or animals

Abstract

A method for labeling an object, which is effective when multiple types of labels are given as necessary even to a very small object such as a fine particulate substrate for use in fixation of biological substances such as probe molecules or nucleic acid primers that are used for a bioassay is provided. Further, an object given the labels is provided. Multiple types of labels can be given as necessary even to very small objects by using materials for labeling prepared in accordance with the composition condition of contained atoms corresponding to at least binary system n-digit numerical value information using a plurality of types (n types) of atoms selected beforehand as part of materials constituting the object, and presence/absence of the selected individual atoms contained or the level of the contents thereof. Further, the bioassay can be performed by the object labeled by the labeling method.

Claims

1. An object to which an biological substance is bound,

wherein the biological substance is bound to the surface of the object,

the object is given a label,

the label includes at least two types of atoms selected from a plurality of types of atoms selected beforehand, and

the label is identified by at least any of mass spectrometry, X-ray photoelectron spectroscopy and Auger electron spectroscopy.

2. The biological substance bound object according to claim 1, wherein the biological substance is a probe.

3. The biological substance bound object according to claim 1, wherein the biological substance is a nucleic acid primer.

7. The biological substance bound object according to claim 1, wherein the shape of the object as a label target is selected from particles of indeterminate forms, particles of determinate forms, fibers and sheets.

8. The biological substance bound object according to claim 7, wherein the object is a magnetic material.

9. The biological substance bound object according to claim 2, wherein the probe is one of a pair of substances selected from nucleic acids, DNAs, RNAs, cDNAs, cRNAs, oligodeoxyribonucleotides, polydeoxyribonucleotides, oligoribonucleotides, polyribonucleotides, peptide nucleic acids (PNAs), oligopeptide nucleic acids, peptides, oligopeptides, polypeptides, proteins, antigens, antibodies enzymes, ligands, ligand receptors, sugars and sugar chains and

capable of being bound with the substances recognizing each other.

13. A method for identifying, detecting or quantitatively measuring a probe bound to the probe bound object according to claim 3,

wherein the type of the object, specifically the type of probe bound to the object is discriminated by

using a label of the object given using the label element, and identifying the presence/absence of individual atoms contained or the level of the contents thereof for the plurality of types of atoms selected beforehand in the composition possessed by the label element using detection means for detecting the presence/absence of the atom contained or the level of the content thereof for the plurality of types of atoms selected beforehand,

discriminating the composition condition of the contained atoms which is satisfied in the composition of the label element, and extracting corresponding at least binary system n-digit numerical value information, and

identifying the type of the object based on the discrete identification information expressed as the at least binary system n-digit numerical value information, and

the probe bound to the object for which the discrimination of the type is performed is detected or quantitatively measured using, as an indicator originating from the probe, atoms, molecules or substances which are contained in the probe but are not contained in the object.

14. The nucleic acid primer bound object according to claim 3, wherein the nucleic acid primer is selected from the group consisting of oligodeoxyribonucleotides, polydeoxyribonucleotides, oligoribonucleotides and polyribonucleotides.

15. The nucleic acid primer bound object according to claim 14, the nucleic acid primer is bound covalently to the surface of the object directly or indirectly via a linker at the 5′

terminal side of the primer.

16. A method for identifying, detecting or quantitatively measuring a nucleic acid primer bound to the nucleic acid primer bound object according to claim 3,

wherein the type of the object, specifically the type of nucleic acid primer bound to the object is discriminated by

using a label of the object given using the label element, and identifying the presence/absence of individual atoms contained or the level of the contents thereof for the plurality of types of atoms selected beforehand in the composition possessed by the label element using detection means for detecting the presence/absence of the atom contained or the level of the content thereof for the plurality of types of atoms selected beforehand,

discriminating the composition condition of the contained atoms which is satisfied in the composition of the label element, and extracting corresponding at least binary system n-digit numerical value information, and

identifying the type of the object based on the discrete identification information expressed as the at least binary system n-digit numerical value information, and

the nucleic acid primer bound to the object for which the discrimination of the type is performed is detected or quantitatively measured using, as an indicator originating from the nucleic acid primer, atoms, molecules or substances which are contained in the nucleic acid primer but are not contained in the object.

4. An object to which an biological substance is bound,

wherein the biological substance is bound to the surface of the object,

the object is given a label,

the label gives discrete identification information allowing individual objects, specifically individual biological substances to be discriminated for a plurality of objects as label targets, specifically a plurality of biological substances bound to the objects, and

the composition condition of contained atoms corresponding to binary system n-digit numerical value information is formed using the number (n) of types of atoms selected beforehand and the presence/absence of the selected individual atoms contained,

whereupon using a label element having a composition satisfying the composition condition of contained atoms,

the discrete identification information expressed as the binary system n-digit numerical value information is given.

6. The biological substance bound object according to claim 4,

wherein in the label,

the number (n) of types of atoms selected beforehand is 5 or more, and the number of types of numerical value information expressed by the number (n) of types of the atoms and the contents of the selected individual atoms is 31 or more.

10. A method for discriminating the type of biological substance bound object given the label according to claim 4, specifically the type of an biological substance bound to the object,

wherein the composition condition of contained atoms corresponding to at least binary system n-digit numerical value information using the number (n) of types of atoms selected beforehand and the presence/absence of the selected individual atoms contained or the level of the contents thereof,

whereupon using labels given to the individual objects using label elements having compositions satisfying the composition condition of the contained atoms,

the presence/absence of individual atoms contained or the level of the contents thereof is identified for the plurality of types of atoms selected beforehand in the composition possessed by the label element using detection means for detecting the presence/absence of the atom contained or the level of the content thereof for the plurality of types of atoms selected beforehand,

the composition condition of the contained atoms which is satisfied in the composition of the label element is discriminated, and corresponding at least binary system n-digit numerical value information is extracted, and

the types of individual biological substance bound objects are identified based on the discrete identification information expressed as the at least binary system n-digit numerical value information.

11. The method for discriminating an biological substance bound object according to claim 10, wherein as detection means for detecting the presence/absence of the atom or the level of the content thereof for each of the plurality of types of atoms selected beforehand, at least one selected from mass spectrometry, X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) is used.

12. The method for discriminating an biological substance bound object according to claim 10, wherein if an object is situated on a flat surface, a step of two-dimensionally imaging the flat surface on which the object is situated is further provided for identifying the position of the object on the flat surface when identifying the presence/absence of the individual atoms contained or the level of the contents thereof for the plurality of types of atoms selected beforehand in the composition possessed by the label element.

5. An object to which an biological substance is bound,

wherein the biological substance is bound to the surface of the object,

the object is given a label,

the label gives discrete identification information allowing individual objects, specifically individual biological substances to be discriminated for a plurality of objects as label targets, specifically a plurality of biological substances bound to the objects, and

the composition condition of contained atoms corresponding to at least binary system n-digit numerical value information is formed using the number (n) of types of atoms selected beforehand and the level of contents of the selected individual atoms,

whereupon using a label element having a composition satisfying the composition condition of contained atoms,

the discrete identification information expressed as the at least binary system n-digit numerical value information is given.