U.S. patent application number 10/021050 was filed with the patent office on 2002-05-23 for biochemical analysis unit and biochemical analyzing method using the same.
This patent application is currently assigned to FUJI PHOTO FILMS CO., LTD.. Invention is credited to Ogura, Nobuhiko.
Application Number | 20020061534 10/021050 |
Document ID | / |
Family ID | 27344246 |
Filed Date | 2002-05-23 |
United States Patent
Application |
20020061534 |
Kind Code |
A1 |
Ogura, Nobuhiko |
May 23, 2002 |
Biochemical analysis unit and biochemical analyzing method using
the same
Abstract
A biochemical analysis unit includes a substrate made of a
material capable of attenuating radiation energy and/or light
energy and formed with a plurality of holes, and a plurality of
absorptive regions formed by forming an absorptive region in every
hole. According to the thus constituted biochemical analysis unit,
even in the case where the absorptive regions are formed at a high
density, when a stimulable phosphor layer formed on a stimulable
phosphor sheet is exposed to a radioactive labeling substance
contained in the plurality of absorptive regions, electron beams
(.beta. rays) released from the radioactive labeling substance
contained in the individual absorptive regions are reliably
prevented from being scattered in the substrate and advancing to
regions of the stimulable phosphor layer that should be exposed to
electron beams released from absorptive regions formed in
neighboring holes. Therefore, it is possible to efficiently prevent
noise caused by the scattering of electron beams released from the
radioactive labeling substance from being generated in biochemical
analysis data produced by irradiating the stimulable phosphor layer
exposed to the radioactive labeling substance with a stimulating
ray and photoelectrically detecting stimulated emission released
from the stimulable phosphor layer and to produce biochemical
analysis data having a high quantitative accuracy.
Inventors: |
Ogura, Nobuhiko; (Kanagawa,
JP) |
Correspondence
Address: |
SUGHRUE, MION, ZINN, MACPEAK & SEAS, PLLC
2100 Pennsylvania Avenue, N.W.
Washington
DC
20037-3202
US
|
Assignee: |
FUJI PHOTO FILMS CO., LTD.
|
Family ID: |
27344246 |
Appl. No.: |
10/021050 |
Filed: |
December 19, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10021050 |
Dec 19, 2001 |
|
|
|
09918500 |
Aug 1, 2001 |
|
|
|
Current U.S.
Class: |
435/6.11 ;
427/2.11; 435/287.2; 435/6.1; 435/7.9 |
Current CPC
Class: |
G01N 21/6452 20130101;
G01N 21/6428 20130101; G01N 21/253 20130101; G01N 21/76 20130101;
G01N 33/54366 20130101 |
Class at
Publication: |
435/6 ; 435/7.9;
435/287.2; 427/2.11 |
International
Class: |
C12Q 001/68; G01N
033/53; G01N 033/542; C12M 001/34; B05D 003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 2, 2000 |
JP |
2000-234776 |
Mar 30, 2001 |
JP |
2001-100942 |
Jun 29, 2001 |
JP |
2001-199183 |
Claims
1. A biochemical analysis unit comprising a substrate made of a
material capable of attenuating radiation energy and/or light
energy and formed with a plurality of holes, and a plurality of
absorptive regions formed by forming an absorptive region in every
hole.
2. A biochemical analysis unit comprising a substrate made of a
material capable of attenuating radiation energy and/or light
energy and formed with a plurality of holes, and a plurality of
absorptive regions formed by forming an absorptive region in every
hole, the plurality of absorptive regions being selectively labeled
with at least one kind of labeling substance selected from a group
consisting of a radioactive labeling substance, a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate and a fluorescent substance
by spotting specific binding substances whose sequence, base
length, composition and the like are known therein and specifically
binding a substance derived from a living organism and labeled with
at least one kind of said labeling substance with the specific
binding substances.
3. A biochemical analysis unit in accordance with claim 2 wherein
the substance derived from a living organism is specifically bound
with specific binding substances by a reaction selected from a
group consisting of hybridization, antigen-antibody reaction and
receptor-ligand reaction.
4. A biochemical analysis unit in accordance with claim 1 wherein
the plurality of absorptive regions are formed by charging an
absorptive material in the plurality of holes formed in the
substrate.
5. A biochemical analysis unit in accordance with claim 2 wherein
the plurality of absorptive regions are formed by charging an
absorptive material in the plurality of holes formed in the
substrate.
6. A biochemical analysis unit in accordance with claim 1 wherein
each of the plurality of holes is formed as a through-hole.
7. A biochemical analysis unit in accordance with claim 2 wherein
each of the plurality of holes is formed as a through-hole.
8. A biochemical analysis unit in accordance with claim 1 wherein
each of the plurality of holes is formed as a recess.
9. A biochemical analysis unit in accordance with claim 2 wherein
each of the plurality of holes is formed as a recess.
10. A biochemical analysis unit in accordance with claim 1 wherein
the substrate is formed of a flexible material.
11. A biochemical analysis unit in accordance with claim 2 wherein
the substrate is formed of a flexible material.
12. A biochemical analysis unit in accordance with claim 1 wherein
the substrate is formed with a gripping portion by which the
substrate can be gripped.
13. A biochemical analysis unit in accordance with claim 2 wherein
the substrate is formed with a gripping portion by which the
substrate can be gripped.
14. A biochemical analysis unit comprising an absorptive substrate
formed of an absorptive material and a perforated plate formed with
a plurality of through-holes and made of a material capable of
attenuating radiation energy and light energy, the perforated plate
being closely contacted with at least one surface of the absorptive
substrate to form a plurality of absorptive regions of the
absorptive substrate in the plurality of through-holes formed in
the perforated plate.
15. A biochemical analysis unit in accordance with claim 14 wherein
perforated plates are in close contact with the both surfaces of
the absorptive substrate.
16. A biochemical analysis unit in accordance with claim 14 wherein
the perforated plate is formed with a gripping portion by which the
perforated plate can be gripped.
17. A biochemical analysis unit in accordance with claim 14 wherein
the plurality of absorptive regions are selectively labeled with at
least one kind of labeling substances selected from a group
consisting of a radioactive labeling substance, a labeling
substance capable of generating chemiluminescent emission when it
contacts a chemiluminescent substrate and/or a fluorescent
substance by spotting specific binding substances whose sequence,
base length, composition and the like are known therein and
hybridizing a substance derived from a living organism and labeled
with at least one kind of labeling substance with the specific
binding substances.
18. A biochemical analysis unit in accordance with claim 1 which is
formed with 10 or more holes.
19. A biochemical analysis unit in accordance with claim 2 which is
formed with 10 or more holes.
20. A biochemical analysis unit in accordance with claim 14 which
is formed with 10 or more holes.
21. A biochemical analysis unit in accordance with claim 18 which
is formed with 1,000 or more holes.
22. A biochemical analysis unit in accordance with claim 19 which
is formed with 1,000 or more holes.
23. A biochemical analysis unit in accordance with claim 20 which
is formed with 1,000 or more holes.
24. A biochemical analysis unit in accordance with claim 21 which
10,000 or more holes.
25. A biochemical analysis unit in accordance with claim 22 which
10,000 or more holes.
26. A biochemical analysis unit in accordance with claim 23 which
10,000 or more holes.
27. A biochemical analysis unit in accordance with claim 1 wherein
each of the plurality of holes has a size of less than 5
mm.sup.2.
28. A biochemical analysis unit in accordance with claim 2 wherein
each of the plurality of holes has a size of less than 5
mm.sup.2.
29. A biochemical analysis unit in accordance with claim 14 wherein
each of the plurality of holes has a size of less than 5
mm.sup.2.
30. A biochemical analysis unit in accordance with claim 27 wherein
each of the plurality of holes has a size of less than 1
mm.sup.2.
31. A biochemical analysis unit in accordance with claim 28 wherein
each of the plurality of holes has a size of less than 1
mm.sup.2.
32. A biochemical analysis unit in accordance with claim 29 wherein
each of the plurality of holes has a size of less than 1
mm.sup.2.
33. A biochemical analysis unit in accordance with claim 30 wherein
each of the plurality of holes has a size of less than 0.1
mm.sup.2.
34. A biochemical analysis unit in accordance with claim 31 wherein
each of the plurality of holes has a size of less than 0.1
mm.sup.2.
35. A biochemical analysis unit in accordance with claim 32 wherein
each of the plurality of holes has a size of less than 0.1
mm.sup.2.
36. A biochemical analysis unit in accordance with claim 1 wherein
the plurality of holes are formed at a density of 10 or more per
cm.sup.2.
37. A biochemical analysis unit in accordance with claim 2 wherein
the plurality of holes are formed at a density of 10 or more per
cm.sup.2.
38. A biochemical analysis unit in accordance with claim 14 wherein
the plurality of holes are formed at a density of 10 or more per
cm.sup.2.
39. A biochemical analysis unit in accordance with claim 36 wherein
the plurality of holes are formed at a density of 1,000 or more per
cm.sup.2.
40. A biochemical analysis unit in accordance with claim 37 wherein
the plurality of holes are formed at a density of 1,000 or more per
cm.sup.2.
41. A biochemical analysis unit in accordance with claim 38 wherein
the plurality of holes are formed at a density of 1,000 or more per
cm.sup.2.
42. A biochemical analysis unit in accordance with claim 39 wherein
the plurality of holes are formed at a density of 10,000 or more
per cm.sup.2.
43. A biochemical analysis unit in accordance with claim 40 wherein
the plurality of holes are formed at a density of 10,000 or more
per cm.sup.2.
44. A biochemical analysis unit in accordance with claim 41 wherein
the plurality of holes are formed at a density of 10,000 or more
per cm.sup.2.
45. A biochemical analysis unit in accordance with claim 1 wherein
the material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to 1/5 or less when the radiation and/or light travels in the
material by a distance equal to that between neighboring absorptive
regions.
46. A biochemical analysis unit in accordance with claim 2 wherein
the material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to 1/5 or less when the radiation and/or light travels in the
material by a distance equal to that between neighboring absorptive
regions.
47. A biochemical analysis unit in accordance with claim 14 wherein
the material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to 1/5 or less when the radiation and/or light travels in the
material by a distance equal to that between neighboring absorptive
regions.
48. A biochemical analysis unit in accordance with 45 wherein the
material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to {fraction (1/10)} or less when the radiation and/or light
travels in the material by a distance equal to that between
neighboring absorptive regions.
49. A biochemical analysis unit in accordance with 46 wherein the
material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to {fraction (1/10)} or less when the radiation and/or light
travels in the material by a distance equal to that between
neighboring absorptive regions.
50. A biochemical analysis unit in accordance with 47 wherein the
material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to {fraction (1/10)} or less when the radiation and/or light
travels in the material by a distance equal to that between
neighboring absorptive regions.
51. A biochemical analysis unit in accordance with 48 wherein the
material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to {fraction (1/100)} or less when the radiation and/or light
travels in the material by a distance equal to that between
neighboring absorptive phosphor layer regions.
52. A biochemical analysis unit in accordance with 49 wherein the
material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to {fraction (1/100)} or less when the radiation and/or light
travels in the material by a distance equal to that between
neighboring absorptive phosphor layer regions.
53. A biochemical analysis unit in accordance with 50 wherein the
material capable of attenuating radiation energy and/or light
energy has a property of reducing the energy of radiation and/or
light to {fraction (1/100)} or less when the radiation and/or light
travels in the material by a distance equal to that between
neighboring absorptive phosphor layer regions.
54. A biochemical analysis unit in accordance with claim 45 wherein
the substrate is formed of a material selected from a group
consisting of metal material, ceramic material and plastic
material.
55. A biochemical analysis unit in accordance with claim 46 wherein
the substrate is formed of a material selected from a group
consisting of metal material, ceramic material and plastic
material.
56. A biochemical analysis unit in accordance with claim 47 wherein
the substrate is formed of a material selected from a group
consisting of metal material, ceramic material and plastic
material.
57. A biochemical analysis unit in accordance with claim 1 wherein
the absorptive region is formed of a porous material.
58. A biochemical analysis unit in accordance with claim 2 wherein
the absorptive region is formed of a porous material.
59. A biochemical analysis unit in accordance with claim 14 wherein
the absorptive substrate is formed of a porous material.
60. A biochemical analysis unit in accordance with claim 57 wherein
the porous material includes a carbon material or a material
capable of forming a membrane filter.
61. A biochemical analysis unit in accordance with claim 58 wherein
the porous material includes a carbon material or a material
capable of forming a membrane filter.
62. A biochemical analysis unit in accordance with claim 59 wherein
the porous material includes a carbon material or a material
capable of forming a membrane filter.
63. A biochemical analysis unit in accordance with claim 1 wherein
the absorptive region is formed of a fiber material.
64. A biochemical analysis unit in accordance with claim 2 wherein
the absorptive region is formed of a fiber material.
65. A biochemical analysis unit in accordance with claim 14 wherein
the absorptive substrate is formed of a fiber material.
66. A biochemical analyzing method comprising the steps of
preparing a biochemical analysis unit by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions, each
of which is formed in a plurality of holes formed in a substrate
made of a material capable of attenuating radiation energy and
specifically binding a substance derived from a living organism and
labeled with a radioactive labeling substance with the specific
binding substances, superposing the biochemical analysis unit on a
stimulable phosphor sheet in which a stimulable phosphor layer is
formed so that the stimulable phosphor layer faces the plurality of
absorptive regions, thereby exposing the stimulable phosphor layer
to the radioactive labeling substance contained in the plurality of
absorptive regions, irradiating the stimulable phosphor layer
exposed to the radioactive labeling substance with a stimulating
ray, thereby exciting stimulable phosphor contained in the
stimulable phosphor layer, photoelectrically detecting stimulated
emission released from the stimulable phosphor contained in the
stimulable phosphor layer, thereby producing biochemical analysis
data, and effecting biochemical analysis based on the biochemical
analysis data.
67. A biochemical analyzing method in accordance with claim 66
wherein a plurality of dot-like stimulable phosphor layer regions
are formed spaced-apart from each other in the stimulable phosphor
sheet in the same pattern as that of the plurality of holes formed
in the substrate of the biochemical analysis unit and the
biochemical analysis unit and the stimulable phosphor sheet are
superposed on each other so that each of the plurality of dot-like
stimulable phosphor layer regions faces one of the plurality of
absorptive regions in the plurality of holes formed in the
substrate of the biochemical analysis unit, thereby exposing the
plurality of dot-like stimulable phosphor layer regions of the
stimulable phosphor sheet to the radioactive labeling substance
contained in the plurality of absorptive regions.
68. A biochemical analyzing method comprising the steps of
preparing a biochemical analysis unit comprising an absorptive
substrate formed of an absorptive material and a perforated plate
made of a material capable of attenuating radiation energy and
light energy and formed with a plurality of through-holes, the
perforated plate being closely contacted with at least one surface
of the absorptive substrate to form a plurality of absorptive
regions of the absorptive substrate in the plurality of
through-holes formed in the perforated plate, the plurality of
absorptive regions being selectively labeled with a radioactive
labeling substance by spotting specific binding substances, which
can specifically bind with a substance derived from a living
organism and whose sequence, base length, composition and the like
are known, in the plurality of absorptive regions and specifically
binding a substance derived from a living organism and labeled with
a radioactive labeling substance, superposing the biochemical
analysis unit and a stimulable phosphor sheet in which a stimulable
phosphor layer is formed via the perforated plate so that the
stimulable phosphor layer faces the plurality of absorptive
regions, thereby exposing the stimulable phosphor layer to the
radioactive labeling substance contained in the plurality of
absorptive regions, irradiating the stimulable phosphor layer
exposed to the radioactive labeling substance with a stimulating
ray to excite stimulable phosphor contained in the stimulable
phosphor layer, photoelectrically detecting stimulated emission
released from the stimulable phosphor contained in the stimulable
phosphor layer to produce biochemical analysis data, and effecting
biochemical analysis based on the biochemical analysis data.
69. A biochemical analyzing method in accordance with claim 68
wherein a plurality of dot-like stimulable phosphor layer regions
are formed spaced-apart in the stimulable phosphor sheet in the
same pattern as that of the plurality of through-holes formed in
the perforated plate, and the biochemical analysis unit and the
stimulable phosphor sheet are superposed on each other so that each
of the plurality of dot-like stimulable phosphor layer regions
faces one of the plurality of absorptive regions via one of the
through-holes formed in the perforated plate, thereby exposing the
plurality of dot-like stimulable phosphor layer regions to a
radioactive labeling substance contained in the plurality of
absorptive regions.
70. A biochemical analyzing method comprising the steps of
preparing a biochemical analysis unit by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions formed
in a plurality of holes formed in a substrate made of a material
capable of attenuating light energy and specifically binding a
substance derived from a living organism and labeled with a
fluorescent substance with the specific binding substances, thereby
selectively labeling a plurality of absorptive regions, irradiating
the biochemical analysis unit with a stimulating ray, thereby
exciting the fluorescent substance, photoelectrically detecting
fluorescence released from the fluorescent substance, thereby
producing biochemical analysis data, and effecting biochemical
analysis based on the biochemical analysis data.
71. A biochemical analyzing method comprising the steps of
preparing a biochemical analysis unit by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions formed
in a plurality of holes formed in a substrate made of a material
capable of attenuating light energy and specifically binding a
substance derived from a living organism and labeled with a
labeling substance capable of generating chemiluminescent emission
when it contacts a chemiluminescent substrate with the specific
binding substances, thereby selectively labeling the plurality of
absorptive regions, bringing the biochemical analysis unit into
close contact with a chemiluminescent substrate, photoelectrically
detecting chemiluminescent emission released from the labeling
substance, thereby producing biochemical analysis data, and
effecting biochemical analysis based on the biochemical analysis
data.
72. A biochemical analyzing method comprising the steps of
preparing a biochemical analysis unit by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions formed
in a plurality of holes formed in a substrate made of a material
capable of attenuating light energy and specifically binding a
substance derived from a living organism and labeled with a
fluorescent substance and a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate with the specific binding substances,
thereby selectively labeling the plurality of absorptive regions,
irradiating the biochemical analysis unit with a stimulating ray to
excite the fluorescent substance, and photoelectrically detecting
fluorescence released from the fluorescent substance, thereby
producing biochemical analysis data, while bringing the biochemical
analysis unit into close contact with a chemiluminescent substrate,
photoelectrically detecting chemiluminescent emission released from
the labeling substance, thereby producing biochemical analysis
data, and effecting biochemical analysis based on the biochemical
analysis data.
73. A biochemical analyzing method comprising the steps of bringing
an absorptive substrate made of an absorptive material and formed
with a plurality of absorptive regions by spotting thereon specific
binding substances, which can specifically bind with a substance
derived from a living organism and whose sequence, base length,
composition and the like are known, the plurality of the absorptive
regions being selectively labeled by specifically binding a
substance derived from a living organism and labeled with a
fluorescent substance with the specific binding substances
contained in the plurality of absorptive regions, into close
contact with a perforated plate made of a material capable of
attenuating light energy and formed with a plurality of
through-holes at positions corresponding to the plurality of
absorptive regions formed in the absorptive substrate, irradiating
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate to stimulate the fluorescent substance,
photoelectrically detecting fluorescence released from the
fluorescent substance, thereby producing biochemical analysis data,
and effecting biochemical analysis based on the biochemical
analysis data.
74. A biochemical analyzing method comprising the steps of bringing
an absorptive substrate made of an absorptive material and formed
with a plurality of absorptive regions by spotting thereon specific
binding substances, which can specifically bind with a substance
derived from a living organism and whose sequence, base length,
composition and the like are known, the plurality of the absorptive
regions being selectively labeled by specifically binding a
substance derived from a living organism and labeled with a
labeling substance capable of generating chemiluminescent emission
when it contacts a chemiluminescent substrate with the specific
binding substances contained in the plurality of absorptive
regions, into close contact with a perforated plate made of a
material capable of attenuating light energy and formed with a
plurality of through-holes at positions corresponding to the
plurality of absorptive regions formed in the absorptive substrate,
bringing a chemiluminescent substrate into close contact with the
plurality of absorptive regions formed in the absorptive substrate
through the plurality of through-holes formed in the perforated
plate, photoelectrically detecting chemiluminescent emission
released from the labeling substance, thereby producing biochemical
analysis data, and effecting biochemical analysis based on the
biochemical analysis data.
75. A biochemical analyzing method comprising the steps of bringing
an absorptive substrate made of an absorptive material and formed
with a plurality of absorptive regions by spotting thereon specific
binding substances, which can specifically bind with a substance
derived from a living organism and whose sequence, base length,
composition and the like are known, the plurality of the absorptive
regions being selectively labeled by specifically binding a
substance derived from a living organism and labeled with a
fluorescent substance and a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate with the specific binding substances
contained in the plurality of absorptive regions, into close
contact with a perforated plate made of a material capable of
attenuating light energy and formed with a plurality of
through-holes at positions corresponding to the plurality of
absorptive regions formed in the absorptive substrate, irradiating
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate to stimulate the fluorescent substance, and
photoelectrically detecting fluorescence released from the
fluorescent substance, thereby producing biochemical analysis data,
while bringing a chemiluminescent substrate into close contact with
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate, and photoelectrically detecting chemiluminescent
emission released from the labeling substance, thereby producing
biochemical analysis data, and effecting biochemical analysis based
on the biochemical analysis data.
76. A biochemical analyzing method comprising the steps of
preparing a stimulable phosphor sheet including a support,
selectively storing radiation energy in a plurality of stimulable
phosphor layer regions formed at least one-dimensionally and
spaced-apart from each other in the support, moving the stimulable
phosphor sheet and a stimulating ray relative to each other in at
least a main scanning direction, sequentially irradiating the
plurality of stimulable phosphor layer regions with the stimulating
ray, thereby exciting stimulable phosphor contained in the
plurality of stimulable phosphor layer regions, photoelectrically
detecting stimulated emission released from the stimulable
phosphor, thereby producing analog data, converting the analog data
to digital data and producing biochemical analysis data.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to a biochemical analysis unit
and a biochemical analyzing method using the same and,
particularly, to a biochemical analysis unit and a biochemical
analyzing method which can prevent noise caused by the scattering
of electron beams released from a radioactive labeling substance
from being generated in biochemical analysis data even in the case
of forming spots of specific binding substances on the surface of a
carrier at a high density, which can specifically bind with a
substance derived from a living organism and whose sequence, base
length, composition and the like are known, specifically binding
the spot-like specific binding substances with a substance derived
from a living organism labeled with a radioactive substance to
selectively label the spot-like specific binding substances with
the radioactive substance, thereby obtaining a biochemical analysis
unit, superposing the thus obtained biochemical analysis unit and a
stimulable phosphor layer, exposing the stimulable phosphor layer
to the radioactive labeling substance, irradiating the stimulable
phosphor layer with a stimulating ray to excite the stimulable
phosphor, photoelectrically detecting the stimulated emission
released from the stimulable phosphor layer to produce biochemical
analysis data, and analyzing the substance derived from a living
organism; and can prevent noise caused by the scattering of
chemiluminescent emission and/or fluorescence released from a
labeling substance which generates chemiluminescent emission when
it contacts a chemiluminescent substrate and/or a fluorescent
substance from being generated in biochemical analysis data even in
the case of forming spots of specific binding substances on the
surface of a carrier at high density, which can specifically bind
with a substance derived from a living organism and whose sequence,
base length, composition and the like are known, specifically
binding the spot-like specific binding substance with a substance
derived from a living organism labeled with, in addition to a
radioactive labeling substance or instead of a radioactive labeling
substance, a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate and/or a
fluorescent substance to selectively label the spot-like specific
binding substances therewith, thereby obtaining a biochemical
analysis unit, photoelectrically detecting chemiluminescent
emission and/or fluorescence released from the biochemical analysis
unit to produce biochemical analysis data, and analyzing the
substance derived from a living organism.
DESCRIPTION OF THE PRIOR ART
[0002] An autoradiographic analyzing system using as a detecting
material for detecting radiation a stimulable phosphor which can
absorb, store and record the energy of radiation when it is
irradiated with radiation and which, when it is then stimulated by
an electromagnetic wave having a specified wavelength, can release
stimulated emission whose light amount corresponds to the amount of
radiation with which it was irradiated is known, which comprises
the steps of introducing a radioactively labeled substance into an
organism, using the organism or a part of the tissue of the
organism as a specimen, superposing the specimen and a stimulable
phosphor sheet formed with a stimulable phosphor layer for a
certain period of time, storing and recording radiation energy in a
stimulable phosphor contained in the stimulable phosphor layer,
scanning the stimulable phosphor layer with an electromagnetic wave
to excite the stimulable phosphor, photoelectrically detecting the
stimulated emission released from the stimulable phosphor to
produce digital image signals, effecting image processing on the
obtained digital image signals, and reproducing an image on
displaying means such as a CRT or the like or a photographic film
(see, for example, Japanese Patent Publication No. 1-60784,
Japanese Patent Publication No. 1-60782, Japanese Patent
Publication No. 4-3952 and the like).
[0003] Unlike the system using a photographic film, according to
the autoradiographic analyzing system using the stimulable phosphor
as a detecting material, development, which is chemical processing,
becomes unnecessary. Further, it is possible reproduce a desired
image by effecting image processing on the obtained image data and
effect quantitative analysis using a computer. Use of a stimulable
phosphor in these processes is therefore advantageous.
[0004] On the other hand, a fluorescence analyzing system using a
fluorescent substance as a labeling substance instead of a
radioactive labeling substance in the autoradiographic analyzing
system is known. According to this system, it is possible to study
a genetic sequence, study the expression level of a gene, and to
effect separation or identification of protein or estimation of the
molecular weight or properties of protein or the like. For example,
this system can perform a process including the steps of
distributing a plurality of DNA fragments on a gel support by means
of electrophoresis after a fluorescent dye was added to a solution
containing a plurality of DNA fragments to be distributed, or
distributing a plurality of DNA fragments on a gel support
containing a fluorescent dye, or dipping a gel support on which a
plurality of DNA fragments have been distributed by means of
electrophoresis in a solution containing a fluorescent dye, thereby
labeling the electrophoresed DNA fragments, exciting the
fluorescent dye by a stimulating ray to cause it to release
fluorescent light, detecting the released fluorescent light to
produce an image and detecting the distribution of the DNA
fragments on the gel support. This system can also perform a
process including the steps of distributing a plurality of DNA
fragments on a gel support by means of electrophoresis, denaturing
the DNA fragments, transferring at least a part of the denatured
DNA fragments onto a transfer support such as a nitrocellulose
support by the Southern-blotting method, hybridizing a probe
prepared by labeling target DNA and DNA or RNA complementary
thereto with the denatured DNA fragments, thereby selectively
labeling only the DNA fragments complementary to the probe DNA or
probe RNA, exciting the fluorescent dye by a stimulating ray to
cause it to release fluorescent light, detecting the released
fluorescent light to produce an image and detecting the
distribution of the target DNA on the transfer support. This system
can further perform a process including the steps of preparing a
DNA probe complementary to DNA containing a target gene labeled by
a labeling substance, hybridizing it with DNA on a transfer
support, combining an enzyme with the complementary DNA labeled by
a labeling substance, causing the enzyme to contact a fluorescent
substance, transforming the fluorescent substance to a fluorescent
substance having fluorescent light releasing property, exciting the
thus produced fluorescent substance by a stimulating ray to release
fluorescent light, detecting the fluorescent light to produce an
image and detecting the distribution of the target DNA on the
transfer support. This fluorescence detecting system is
advantageous in that a genetic sequence or the like can be easily
detected without using a radioactive substance.
[0005] Similarly, there is known a chemiluminescence detecting
system comprising the steps of fixing a substance derived from a
living organism such as a protein or a nucleic acid sequence on a
support, selectively labeling the substance derived from a living
organism with a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate, contacting
the substance derived from a living organism and selectively
labeled with the labeling substance and the chemiluminescent
substrate, photoelectrically detecting the chemiluminescent
emission in the wavelength of visible light generated by the
contact of the chemiluminescent substrate and the labeling
substance to produce digital image signals, effecting image
processing thereon, and reproducing a chemiluminescent image on a
display means such as a CRT or a recording material such as a
photographic film, thereby obtaining information relating to the
high molecular substance such as genetic information
[0006] Further, a micro-array analyzing system has been recently
developed, which comprises the steps of using a spotting device to
drop at different positions on the surface of a carrier such as a
slide glass plate, a membrane filter or the like specific binding
substances, which can specifically bind with a substance derived
from a living organism such as a hormone, tumor marker, enzyme,
antibody, antigen, abzyme, other protein, a nuclear acid, cDNA,
DNA, RNA or the like and whose sequence, base length, composition
and the like are known, thereby forming a number of independent
spots, specifically binding the specific binding substances using a
hybridization method or the like with a substance derived from a
living organism such as a hormone, tumor marker, enzyme, antibody,
antigen, abzyme, other protein, a nuclear acid, cDNA, DNA or mRNA,
which is gathered from a living organism by extraction, isolation
or the like or is further subjected to chemical processing,
chemical modification or the like and which is labeled with a
labeling substance such as a fluorescent substance, dye or the
like, thereby forming a micro-array, irradiating the micro-array
with a stimulating ray, photoelectrically detecting light such as a
fluorescence emitted from a labeling substance such as a
fluorescent substance, dye or the like, and analyzing the substance
derived from a living organism. This micro-array analyzing system
is advantageous in that a substance derived from a living organism
can be analyzed in a short time period by forming a number of spots
of specific binding substances at different positions of the
surface of a carrier such as a slide glass plate at high density
and hybridizing them with a substance derived from a living
organism and labeled with a labeling substance.
[0007] In addition, a macro-array analyzing system using a
radioactive labeling substance as a labeling substance has been
further developed, which comprises the steps of using a spotting
device to drop at different positions on the surface of a carrier
such as a membrane filter or the like specific binding substances,
which can specifically bind with a substance derived from a living
organism such as a hormone, tumor marker, enzyme, antibody,
antigen, abzyme, other protein, a nuclear acid, cDNA, DNA, RNA or
the like and whose sequence, base length, composition and the like
are known, thereby forming a number of independent spots,
specifically binding the specific binding substance using a
hybridization method or the like with a substance derived from a
living organism such as a hormone, tumor marker, enzyme, antibody,
antigen, abzyme, other protein, a nuclear acid, cDNA, DNA or mRNA,
which is gathered from a living organism by extraction, isolation
or the like or is further subjected to chemical processing,
chemical modification or the like and which is labeled with a
radioactive labeling substance, thereby forming a macro-array,
superposing the macro-array and a stimulable phosphor sheet formed
with a stimulable phosphor layer, exposing the stimulable phosphor
layer to a radioactive labeling substance, irradiating the
stimulable phosphor layer with a stimulating ray to excite the
stimulable phosphor, photoelectrically detecting the stimulated
emission released from the stimulable phosphor to produce
biochemical analysis data, and analyzing the substance derived from
a living organism.
[0008] However, in the macro-array analyzing system using a
radioactive labeling substance as a labeling substance, when the
stimulable phosphor layer is exposed to a radioactive labeling
substance, since radiation energy of the radioactive labeling
substance contained in spots formed on the surface of a carrier
such as a membrane filter is very large, electron beams released
from the radioactive labeling substance contained in the individual
spots are scattered in the carrier such as a membrane filter,
thereby impinging on regions of the stimulable phosphor layer that
should be exposed to the radioactive labeling substance contained
in neighboring spots, or electron beams released from the
radioactive labeling substance contained in the individual spots
are scattered and mixed with the electron beams released from the
radioactive labeling substance contained in neighboring spots and
then impinge on regions of the stimulable phosphor layer to
generate noise in biochemical analysis data produced by
photoelectrically detecting stimulated emission and to lower the
accuracy of biochemical analysis when a substance derived from a
living organism is analyzed by quantifying the radiation amount of
each spot. The accuracy of biochemical analysis is markedly
degraded when spots are formed closely to each other at high
density.
[0009] In order to solve these problems by preventing noise caused
by the scattering of electron beams released from radioactive
labeling substance contained in neighboring spots, it is inevitably
required to increase the distance between neighboring spots and
this makes the density of the spots lower and the test efficiency
lower.
[0010] Further, in the field of biochemical analysis, it is often
required to analyze a substance derived from a living organism by
specifically binding, using a hybridization method or the like,
specific binding substances spot-like formed at different positions
on the surface of a carrier such as a membrane filter or the like,
which can specifically bind with a substance derived from a living
organism such as a hormone, tumor marker, enzyme, antibody,
antigen, abzyme, other protein, a nuclear acid, cDNA, DNA, RNA or
the like and whose sequence, base length, composition and the like
are known, with a substance derived from a living organism labeled
with, in addition to a radioactive labeling substance, a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate and/or a fluorescent
substance, and after exposing a stimulable phosphor layer to the
radioactive labeling substance or prior to exposing a stimulable
phosphor layer to the radioactive labeling substance, causing it to
contact a chemiluminescent substrate, thereby photoelectrically
detecting the chemiluminescent emission in the wavelength of
visible light, and/or irradiating it with a stimulating ray,
thereby photoelectrically detecting fluorescence released from a
fluorescent substance. In these cases, chemiluminescent emission or
fluorescence released from spots is scattered in the carrier such
as a membrane filter or chemiluminescent emission or fluorescence
released from any particular spot is scattered and mixed with
chemiluminescent emission or fluorescence released from neighboring
spots, thereby generating noise in biochemical analysis data
produced by photoelectrically detecting chemiluminescent emission
and/or fluorescence.
SUMMARY OF THE INVENTION
[0011] It is therefore an object of the present invention to
provide a biochemical analysis unit which can prevent noise caused
by the scattering of electron beams released from a radioactive
labeling substance from being generated in biochemical analysis
data even in the case of forming spots of specific binding
substances on the surface of a carrier at high density, which can
specifically bind with a substance derived from a living organism
and whose sequence, base length, composition and the like are
known, specifically binding the spot-like specific binding
substance with a substance derived from a living organism and
labeled with a radioactive substance to selectively label the
spot-like specific binding substances with a radioactive substance,
thereby obtaining a biochemical analysis unit, superposing the thus
obtained biochemical analysis unit and a stimulable phosphor layer,
exposing the stimulable phosphor layer to the radioactive labeling
substance, irradiating the stimulable phosphor layer with a
stimulating ray to excite the stimulable phosphor,
photoelectrically detecting the stimulated emission released from
the stimulable phosphor layer to produce biochemical analysis data,
and analyzing the substance derived from a living organism.
[0012] It is another object of the present invention to provide a
biochemical analysis unit which can prevent noise caused by the
scattering of chemiluminescent emission and/or fluorescence
released from a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate and/or a
fluorescent substance from being generated in biochemical analysis
data even in the case of forming spots of specific binding
substances on the surface of a carrier at high density, which can
specifically bind with a substance derived from a living organism
and whose sequence, base length, composition and the like are
known, specifically binding the spot-like specific binding
substance with a substance derived from a living organism and
labeled with, in addition to a radioactive labeling substance or
instead of a radioactive labeling substance, a labeling substance
which generates chemiluminescent emission when it contacts a
chemiluminescent substrate and/or a fluorescent substance to
selectively label the spot-like specific binding substances
therewith, thereby obtaining a biochemical analysis unit,
photoelectrically detecting chemiluminescent emission and/or
fluorescence released from the biochemical analysis unit to produce
biochemical analysis data, and analyzing the substance derived from
a living organism.
[0013] It is a further object of the present invention to provide a
biochemical analyzing method which can effect quantitative
biochemical analysis with high accuracy by producing biochemical
analysis data based on a biochemical analysis unit obtained by
forming spots of specific binding substances on the surface of a
carrier at high density, which can specifically bind with a
substance derived from a living organism and whose sequence, base
length, composition and the like are known, specifically binding
the spot-like specific binding substances with a substance derived
from a living organism and labeled with a radioactive labeling
substance, a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate and/or a
fluorescent substance, thereby selectively labeling the spot-like
specific binding substances therewith.
[0014] The above other objects of the present invention can be
accomplished by a biochemical analysis unit comprising a substrate
made of a material capable of attenuating radiation energy and/or
light energy and formed with a plurality of holes, and a plurality
of absorptive regions formed by forming an absorptive region in
every hole.
[0015] In one mode of use of the biochemical analysis unit
according to this aspect of the present invention, specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, are spotted in the absorption regions in a
number of the holes formed in the biochemical analysis unit at a
high density and a substance derived from a living organism and
labeled with a radioactive substance is specifically bound with the
specific binding substances, thereby selectively labeling the
plurality of absorptive regions therewith. The biochemical analysis
unit is then disposed so as to face a stimulable phosphor layer,
thereby exposing the stimulable phosphor layer to the radioactive
labeling substance contained in the plurality of absorptive
regions. Since the substrate of the biochemical analysis unit is
made of a material capable of attenuating radiation energy,
electron beams (.beta. rays) released from the radioactive labeling
substance contained in the individual absorptive regions are
reliably prevented from being scattered in the substrate and
advancing to regions of the stimulable phosphor layer that should
be exposed to electron beams released from absorptive regions
formed in neighboring holes. Therefore, it is possible to
efficiently prevent noise caused by the scattering of electron
beams released from the radioactive labeling substance from being
generated in biochemical analysis data produced by irradiating the
stimulable phosphor layer exposed to the radioactive labeling
substance with a stimulating ray and photoelectrically detecting
stimulated emission released from the stimulable phosphor layer and
to produce biochemical analysis data having a high quantitative
accuracy.
[0016] In another mode of use of the biochemical analysis unit
according to this aspect of the present invention, specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, are spotted in absorption regions in a
number of holes formed in a biochemical analysis unit at a high
density and a substance derived from a living organism and labeled
with a labeling substance which generates chemiluminescent emission
when it contacts a chemiluminescent substrate and/or a fluorescent
substance, instead of with a radioactive labeling substance,
thereby selectively labeling the plurality of absorptive regions
therewith. Biochemical data are then produced by photoelectrically
detecting chemiluminescent emission generated by the contact of a
chemiluminescent substrate and the labeling substance and/or
fluorescence released from the fluorescent substance in response to
irradiation by a stimulating ray. Since the substrate of the
biochemical analysis unit is made of a material capable of
attenuating radiation energy, it is possible to reliably prevent
chemiluminescent emission and/or fluorescence from being scattered
in the substrate and, therefore, it is possible to efficiently
prevent noise caused by the scattering of chemiluminescent emission
and/or fluorescence from being generated in biochemical analysis
data produced by photoelectrically detecting chemiluminescent
emission and/or fluorescence.
[0017] In another mode of use of the biochemical analysis unit
according to this aspect the present invention, specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, are spotted in absorption regions in a
number of holes formed in a biochemical analysis unit at a high
density and a substance derived from a living organism and labeled
with, in addition to a radioactive labeling substance, a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate and/or a fluorescent
substance, thereby selectively labeling the plurality of absorptive
regions therewith. The biochemical analysis unit is then disposed
so as to face a stimulable phosphor layer, thereby exposing the
stimulable phosphor layer to a radioactive labeling substance
contained in the plurality of absorptive regions. Since the
substrate of the biochemical analysis unit is made of a material
capable of attenuating radiation energy, electron beams (.beta.
rays) released from the radioactive labeling substance contained in
the individual absorptive regions are reliably prevented from being
scattered in the substrate and advancing to regions of the
stimulable phosphor layer that should be exposed to electron beams
released from absorptive regions formed in neighboring holes.
Therefore, it is possible to efficiently prevent noise caused by
the scattering of electron beams released from the radioactive
labeling substance from being generated in biochemical analysis
data produced by irradiating the stimulable phosphor layer exposed
to the radioactive labeling substance with a stimulating ray and
photoelectrically detecting stimulated emission released from the
stimulable phosphor layer and to produce biochemical analysis data
having a high quantitative accuracy. On the other hand, when
biochemical data are produced by photoelectrically detecting
chemiluminescent emission generated by the contact of a
chemiluminescent substrate and the labeling substance and/or
fluorescence released from the fluorescent substance in response to
irradiation by a stimulating ray, the fact that the substrate is
made of a material capable of attenuating radiation energy and
light energy makes it possible to reliably prevent chemiluminescent
emission and/or fluorescence from being scattered in the substrate
and, therefore, it is possible to efficiently prevent noise caused
by the scattering of chemiluminescent emission and/or fluorescence
from being generated in biochemical analysis data produced by
photoelectrically detecting chemiluminescent emission and/or
fluorescence.
[0018] The above and other objects of the present invention can
also be accomplished by a biochemical analysis unit comprising a
substrate made of a material capable of attenuating radiation
energy and/or light energy and formed with a plurality of holes,
and a plurality of absorptive regions formed by forming an
absorptive region in every hole, the plurality of absorptive
regions being selectively labeled with at least one kind of
labeling substance selected from a group consisting of a
radioactive labeling substance, a labeling substance which
generates chemiluminescent emission when it contacts a
chemiluminescent substrate and a fluorescent substance by spotting
specific binding substances whose sequence, base length,
composition and the like are known therein and specifically binding
a substance derived from a living organism and labeled with at
least one kind of said labeling substance with the specific binding
substances.
[0019] In the present invention, the case where a substance derived
from a living organism is labeled with a fluorescent substance as
termed herein includes the case where a substance derived from a
living organism is labeled with a fluorescent dye and the case
where a substance derived from a living organism is labeled with a
fluorescent substance obtained by combining an enzyme with a
labeled specimen, contacting the enzyme and a fluorescent
substrate, thereby changing the fluorescent substrate to a
fluorescent substance capable of emitting fluorescent light.
[0020] According to this aspect of the present invention, the
plurality of absorptive regions are selectively labeled with at
least one kind of labeling substance selected from a group
consisting of a radioactive labeling substance, a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate and a fluorescent substance
by spotting therein specific binding substances, which can
specifically bind with a substance derived from a living organism
and whose sequence, base length, composition and the like are known
and specifically binding a substance derived from a living organism
and labeled with at least one kind of said labeling substance with
the specific binding substances. In this case, since the substrate
is made of a material capable of attenuating radiation energy, when
the biochemical analysis unit is disposed so as to face a
stimulable phosphor layer, thereby exposing the stimulable phosphor
layer to a radioactive labeling substance contained in the
plurality of absorptive regions, electron beams (.beta. rays)
released from the radioactive labeling substance contained in the
individual absorptive regions are reliably prevented from being
scattered in the substrate and advancing to regions of the
stimulable phosphor layer that should be exposed to electron beams
released from absorptive regions formed in neighboring holes.
Therefore, it is possible to efficiently prevent noise caused by
the scattering of electron beams released from the radioactive
labeling substance from being generated in biochemical analysis
data produced by irradiating the stimulable phosphor layer exposed
to the radioactive labeling substance with a stimulating ray and
photoelectrically detecting stimulated emission released from the
stimulable phosphor layer and to produce biochemical analysis data
having a high quantitative accuracy.
[0021] Further, according to this aspect of the present invention,
since the substrate is made of a material capable of attenuating
light energy, when biochemical data are produced by
photoelectrically detecting chemiluminescent emission generated by
the contact of a chemiluminescent substrate and the labeling
substance and/or fluorescence released from the fluorescent
substance in response to the irradiation of a stimulating ray, it
is possible to reliably prevent chemiluminescent emission and/or
fluorescence from being scattered in the substrate and, therefore,
it is possible to efficiently prevent noise caused by the
scattering of chemiluminescent emission and/or fluorescence from
being generated in biochemical analysis data produced by
photoelectrically detecting chemiluminescent emission and/or
fluorescence.
[0022] Furthermore, according to this aspect of the present
invention, the substrate is made of a material capable of
attenuating radiation energy and light energy and the plurality of
absorptive regions are selectively labeled with at least one kind
of labeling substances selected from a group consisting of a
radioactive labeling substance, a labeling substance which
generates chemiluminescent emission when it contacts a
chemiluminescent substrate and a fluorescent substance by spotting
therein specific binding substances which can specifically bind
with a substance derived from a living organism and whose sequence,
base length, composition and the like are known, and specifically
binding a substance derived from a living organism and labeled with
at least one kind of said labeling substances with the specific
binding substances. Therefore, when the biochemical analysis unit
is disposed so as to face a stimulable phosphor layer, thereby
exposing the stimulable phosphor layer to the radioactive labeling
substance contained in the plurality of absorptive regions,
electron beams (.beta. rays ) released from the radioactive
labeling substance contained in the individual absorptive regions
are reliably prevented from being scattered in the substrate and
advancing to regions of the stimulable phosphor layer that should
be exposed to electron beams released from absorptive regions
formed in neighboring holes. Therefore, it is possible to
efficiently prevent noise caused by the scattering of electron
beams released from the radioactive labeling substance from being
generated in biochemical analysis data produced by irradiating the
stimulable phosphor layer exposed to the radioactive labeling
substance with a stimulating ray and photoelectrically detecting
stimulated emission released from the stimulable phosphor layer and
to produce biochemical analysis data having a high quantitative
accuracy. On the other hand, when biochemical data are produced by
photoelectrically detecting chemiluminescent emission generated by
the contact of a chemiluminescent substrate and the labeling
substance and/or fluorescence released from the fluorescent
substance in response to the irradiation of a stimulating ray, the
fact that the substrate is made of a material capable of
attenuating radiation energy and light energy makes it possible to
reliably prevent chemiluminescent emission and/or fluorescence from
being scattered in the substrate and, therefore, it is possible to
efficiently prevent noise caused by the scattering of
chemiluminescent emission and/or fluorescence from being generated
in biochemical analysis data produced by photoelectrically
detecting chemiluminescent emission and/or fluorescence.
Furthermore, when biochemical data are produced by
photoelectrically detecting chemiluminescent emission generated by
the contact of a chemiluminescent substrate and the labeling
substance and/or fluorescence released from the fluorescent
substance in response to the irradiation of a stimulating ray, the
fact that the substrate is made of a material capable of
attenuating radiation energy and light energy makes it possible to
reliably prevent chemiluminescent emission and/or fluorescence from
being scattered in the substrate and, therefore, it is possible to
efficiently prevent noise caused by the scattering of
chemiluminescent emission and/or fluorescence from being generated
in biochemical analysis data produced by photoelectrically
detecting chemiluminescent emission and/or fluorescence.
[0023] In a preferred aspect of the present invention, the
plurality of absorptive regions are formed by charging an
absorptive material in the plurality of holes formed in the
substrate.
[0024] In a preferred aspect of the present invention, each of the
plurality of holes is formed as a through-hole.
[0025] In another preferred aspect of the present invention, each
of the plurality of holes is formed as a recess.
[0026] In a preferred aspect of the present invention, the
substrate is formed with a gripping portion by which the substrate
can be gripped.
[0027] According to this preferred aspect of the present invention,
since the substrate is formed with a gripping portion by which the
substrate can be gripped, the biochemical analysis unit can be very
easily handled when specific binding substances are spotted, during
hybridization or during exposure operation.
[0028] The above and other objects of the present invention can
also be accomplished by a biochemical analysis unit comprising an
absorptive substrate formed of an absorptive material and a
perforated plate formed with a plurality of through-holes and made
of a material capable of attenuating radiation energy and light
energy, the perforated plate being closely contacted with at least
one surface of the absorptive substrate to form a plurality of
absorptive regions of the absorptive substrate in the plurality of
through-holes formed in the perforated plate.
[0029] In one mode of use of the biochemical analysis unit
according to this aspect of the present invention, specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, are spotted in the plurality of absorption
regions formed in the absorptive substrate in the plurality of
through-holes of the perforated plate at a high density and a
substance derived from a living organism and labeled with a
radioactive substance is specifically bound with the specific
binding substances, thereby selectively labeling the specific
binding substances therewith. The absorptive substrate is the
disposed so as to face a stimulable phosphor layer via the
perforated plate, thereby exposing the stimulable phosphor layer to
the radioactive labeling substance contained in the plurality of
absorptive regions. Since the perforated plate is made of a
material capable of attenuating radiation energy, electron beams
(.beta. rays) released from the radioactive labeling substance
contained in the individual absorptive regions and electron beams
released from neighboring absorptive regions can be reliably
separated by the perforated plate, thereby reliably preventing
electron beams released from the radioactive labeling substance
contained in the individual absorptive regions from advancing to
regions of the stimulable phosphor layer that should be exposed to
electron beams released from neighboring absorptive regions.
Therefore, it is possible to efficiently prevent noise caused by
the scattering of electron beams released from the radioactive
labeling substance from being generated in biochemical analysis
data produced by irradiating the stimulable phosphor layer exposed
to the radioactive labeling substance with a stimulating ray and
photoelectrically detecting stimulated emission released from the
stimulable phosphor layer and to produce biochemical analysis data
having a high quantitative accuracy.
[0030] In another mode of use of the biochemical analysis unit
according to this aspect of the present invention, specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, are spotted in the plurality of absorption
regions formed in the absorptive substrate in the plurality of
through-holes of the perforated plate at a high density and a
substance derived from a living organism and labeled with a
labeling substance capable of generating chemiluminescent emission
when it contacts a chemiluminescent substrate and/or a fluorescent
substance, thereby selectively labeling the specific binding
substances therewith. Biochemical analysis data are then produced
by photoelectrically detecting chemiluminescent emission generated
by bringing a chemiluminescent substrate into contact with the
absorptive substrate via the perforated plate and/or fluorescence
released from the fluorescent substance in response to irradiation
by a stimulating ray via the perforated plate. Since the perforated
plate is made of a material capable of attenuating light energy,
chemiluminescent emission and/or fluorescence released from the
individual absorptive regions and chemiluminescent emission and/or
fluorescence released from neighboring absorptive regions can be
reliably separated by the perforated plate, thereby reliably
preventing chemiluminescent emission and/or fluorescence released
from the individual absorptive regions from being scattered.
Therefore, it is possible to efficiently prevent noise caused by
the scattering of chemiluminescent emission and/or fluorescence
from being generated in biochemical analysis data produced by
photoelectrically detecting chemiluminescence emission and/or
fluorescence.
[0031] In another mode of use of the biochemical analysis unit
according to this aspect of the invention, specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, are spotted in the absorption regions
formed in the plurality of absorptive substrate in the plurality of
through-holes of the perforated plate at a high density and a
substance derived from a living organism and labeled with at least
one kind of labeling substance selected from a group consisting of
a radioactive labeling substance, a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate and/or a fluorescent substance, thereby
selectively labeling the specific binding substances therewith. The
absorptive substrate is then disposed so as to face a stimulable
phosphor layer via the perforated plate, thereby exposing the
stimulable phosphor layer to a radioactive labeling substance
contained in the plurality of absorptive regions. Since the
perforated plate is made of a material capable of attenuating
radiation energy and light energy, electron beams (.beta. rays )
released from the radioactive labeling substance contained in the
individual absorptive regions and electron beams released from
neighboring absorptive regions can be reliably separated by the
perforated plate, thereby reliably preventing electron beams
released from the radioactive labeling substance contained in the
individual absorptive regions from advancing to regions of the
stimulable phosphor layer that should be exposed to electron beams
released from neighboring absorptive regions. Therefore, it is
possible to efficiently prevent noise caused by the scattering of
electron beams released from the radioactive labeling substance
from being generated in biochemical analysis data produced by
irradiating the stimulable phosphor layer exposed to the
radioactive labeling substance with a stimulating ray and
photoelectrically detecting stimulated emission released from the
stimulable phosphor layer and to produce biochemical analysis data
having a high quantitative accuracy. On the other hand, when
biochemical analysis data are produced by photoelectrically
detecting chemiluminescent emission generated by bringing a
chemiluminescent substrate into contact with the absorptive
substrate via the perforated plate and/or fluorescence released
from the fluorescent substance in response to irradiation by a
stimulating ray via the perforated plate, since the perforated
plate is made of a material capable of attenuating radiation energy
and light energy, chemiluminescent emission and/or fluorescence
released from the individual absorptive regions and
chemiluminescent emission and/or fluorescence released from
neighboring absorptive regions can be reliably separated by the
perforated plate, thereby reliably preventing chemiluminescent
emission and/or fluorescence released from the individual
absorptive regions from being scattered. Therefore, it is possible
to efficiently prevent noise caused by the scattering of
chemiluminescent emission and/or fluorescence from being generated
in biochemical analysis data produced by photoelectrically
detecting chemiluminescence emission and/or fluorescence.
[0032] In a preferred aspect of the present invention, perforated
plates are in close contact with the both surfaces of the
absorptive substrate.
[0033] According to this preferred aspect of the present invention,
since perforated plates are in close contact with the both surfaces
of the absorptive substrate, the strength of the biochemical
analysis unit can be improved.
[0034] In a preferred aspect of the present invention, the
perforated plate is formed with a gripping portion by which the
perforated plate can be gripped.
[0035] According to this preferred aspect of the present invention,
since the perforated plate is formed with a gripping portion by
which the perforated plate can be gripped, the biochemical analysis
unit can be very easily handled when specific binding substances
are spotted, during hybridization or during exposure operation.
[0036] In a preferred aspect of the present invention, the specific
binding substances are spotted through the plurality of
through-holes in the plurality of absorptive regions formed on the
absorptive substrate.
[0037] In a preferred aspect of the present invention, the
plurality of absorptive regions are selectively labeled with at
least one kind of labeling substances selected from a group
consisting of a radioactive labeling substance, a labeling
substance capable of generating chemiluminescent emission when it
contacts a chemiluminescent substrate and/or a fluorescent
substance by spotting specific binding substances whose sequence,
base length, composition and the like are known therein and
hybridizing a substance derived from a living organism and labeled
with at least one kind of labeling substance with the specific
binding substances.
[0038] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of preparing a biochemical analysis unit by spotting
specific binding substances, which can specifically bind with a
substance derived from a living organism and whose sequence, base
length, composition and the like are known, in a plurality of
absorptive regions, each of which is formed in a plurality of holes
formed in a substrate made of a material capable of attenuating
radiation energy and specifically binding a substance derived from
a living organism and labeled with a radioactive labeling substance
with the specific binding substances, superposing the biochemical
analysis unit on a stimulable phosphor sheet in which a stimulable
phosphor layer is formed so that the stimulable phosphor layer
faces the plurality of absorptive regions, thereby exposing the
stimulable phosphor layer to the radioactive labeling substance
contained in the plurality of absorptive regions, irradiating the
stimulable phosphor layer exposed to the radioactive labeling
substance with a stimulating ray, thereby exciting stimulable
phosphor contained in the stimulable phosphor layer,
photoelectrically detecting stimulated emission released from the
stimulable phosphor contained in the stimulable phosphor layer,
thereby producing biochemical analysis data, and effecting
biochemical analysis based on the biochemical analysis data.
[0039] According to this aspect of the present invention, the
biochemical analysis unit is prepared by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions formed
in a plurality of holes formed in a substrate made of a material
capable of attenuating radiation energy and specifically binding a
substance derived from a living organism and labeled with a
radioactive labeling substance with the specific binding
substances, thereby selectively labeling the plurality of
absorptive regions. The biochemical analysis unit is then
superposed on a stimulable phosphor sheet in which a stimulable
phosphor layer is formed so that the stimulable phosphor layer
faces the plurality of absorptive regions, thereby exposing the
stimulable phosphor layer to the radioactive labeling substance
contained in the plurality of absorptive regions. Since the
substrate of the biochemical analysis unit is made of a material
capable of attenuating radiation energy, electron beams (.beta.
rays) released from the radioactive labeling substance contained in
the individual absorptive regions are reliably prevented from being
scattered in the substrate and scattered electron beams are
prevented from advancing to regions of the stimulable phosphor
layer that should be exposed to electron beams released from the
radioactive labeling substance contained absorptive regions formed
in neighboring holes. Therefore, it is possible to efficiently
prevent noise caused by the scattering of electron beams released
from the radioactive labeling substance from being generated in
biochemical analysis data produced by irradiating the stimulable
phosphor layer exposed to the radioactive labeling substance with a
stimulating ray and photoelectrically detecting stimulated emission
released from the stimulable phosphor layer and to effect
biochemical analysis with high quantitative accuracy.
[0040] In a preferred aspect of the present invention, the
plurality of absorptive regions are formed by charging an
absorptive material in the plurality of holes formed in the
substrate of the biochemical analysis unit.
[0041] In a preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as through-holes.
[0042] In another preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as recesses.
[0043] In a preferred aspect of the present invention, a plurality
of dot-like stimulable phosphor layer regions are formed
spaced-apart from each other in the stimulable phosphor sheet in
the same pattern as that of the plurality of holes formed in the
substrate of the biochemical analysis unit and the biochemical
analysis unit and the stimulable phosphor sheet are superposed on
each other so that each of the plurality of dot-like stimulable
phosphor layer regions faces one of the plurality of absorptive
regions in the plurality of holes formed in the substrate of the
biochemical analysis unit, thereby exposing the plurality of
dot-like stimulable phosphor layer regions of the stimulable
phosphor sheet to the radioactive labeling substance contained in
the plurality of absorptive regions.
[0044] According to this preferred aspect of the present invention,
the plurality of dot-like stimulable phosphor layer regions are
formed spaced-apart in the stimulable phosphor sheet in the same
pattern as that of the plurality of holes formed in the substrate
of the biochemical analysis unit and the biochemical analysis unit
and the stimulable phosphor sheet are superposed on each other so
that each of the plurality of dot-like stimulable phosphor layer
regions faces one of the absorptive regions in the plurality of
holes formed in the substrate of the biochemical analysis unit,
thereby exposing the plurality of dot-like stimulable phosphor
layer regions of the stimulable phosphor sheet to the radioactive
labeling substance contained in the plurality of absorptive
regions. It is therefore possible to reliably prevent electron
beams released from the radioactive labeling substance contained in
the individual absorptive regions from being scattered and
advancing to the dot-like stimulable phosphor layer regions facing
neighboring absorptive regions. Therefore, the plurality of
dot-like stimulable phosphor layer regions formed in the stimulable
phosphor sheet can be reliably exposed to the radioactive labeling
substance contained in corresponding absorptive regions, thereby
improving the quantitative accuracy of biochemical analysis.
[0045] In a preferred aspect of the present invention, the
substrate of the biochemical analysis unit is made of a material
capable of attenuating radiation energy and light energy, and the
biochemical analysis is effected based on biochemical analysis data
produced by the steps of preparing the biochemical analysis unit by
specifically binding a substance derived from a living organism and
labeled with a fluorescent substance, in addition to a radioactive
labeling substance, with the specific binding substances, thereby
selectively labeling the plurality of absorptive regions,
irradiating the biochemical analysis unit with a stimulating ray,
thereby stimulating the fluorescent substance, and
photoelectrically detecting fluorescence released from the
fluorescent substance.
[0046] According to this preferred aspect of the present invention,
the substrate of the biochemical analysis unit is made of a
material capable of attenuating radiation energy and light energy,
and the biochemical analysis is effected based on biochemical
analysis data produced by the steps of preparing the biochemical
analysis unit by specifically binding a substance derived from a
living organism and labeled with a fluorescent substance, in
addition to a radioactive labeling substance, with the specific
binding substances, thereby selectively labeling the plurality of
absorptive regions, irradiating the biochemical analysis unit with
a stimulating ray, thereby stimulating the fluorescent substance,
and photoelectrically detecting fluorescence released from the
fluorescent substance. A specimen can therefore be labeled with a
fluorescent substance in addition to a radioactive labeling
substance and, therefore, the utility of biochemical analysis can
be improved.
[0047] In a preferred aspect of the present invention, the
substrate of the biochemical analysis unit is made of a material
capable of attenuating radiation energy and light energy, and the
biochemical analysis is effected based on biochemical analysis data
produced by the steps of preparing the biochemical analysis unit by
specifically binding a substance derived from a living organism and
labeled with a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate, in addition
to a radioactive labeling substance, with the specific binding
substances, thereby selectively labeling the plurality of
absorptive regions, bringing the biochemical analysis unit into
contact with a chemiluminescent substrate, and photoelectrically
detecting chemiluminescent emission released from the labeling
substance.
[0048] According to this preferred aspect of the present invention,
the substrate of the biochemical analysis unit is made of a
material capable of attenuating radiation energy and light energy,
and the biochemical analysis is effected based on biochemical
analysis data produced by the steps of preparing the biochemical
analysis unit by specifically binding a substance derived from a
living organism and labeled with a labeling substance which
generates chemiluminescent emission when it contacts a
chemiluminescent substrate, in addition to a radioactive labeling
substance, with the specific binding substances, thereby
selectively labeling the plurality of absorptive regions, bringing
the biochemical analysis unit into contact with a chemiluminescent
substrate, and photoelectrically detecting chemiluminescent
emission released from the labeling substance. A specimen can
therefore be labeled with a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate in addition to a radioactive labeling
substance and, therefore, the utility of biochemical analysis can
be improved.
[0049] In a preferred aspect of the present invention, the
substrate of the biochemical analysis unit is made of a material
capable of attenuating radiation energy and light energy, and the
biochemical analysis is effected based on biochemical analysis data
produced by the steps of preparing the biochemical analysis unit by
specifically binding a substance derived from a living organism and
labeled with, in addition to a radioactive labeling substance, a
fluorescent substance and a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate with the specific binding substances, thereby selectively
labeling the plurality of absorptive regions, irradiating the
biochemical analysis unit with a stimulating ray to stimulate the
fluorescent substance, and photoelectrically detecting fluorescence
released from the fluorescent substance, while bringing the
biochemical analysis unit into contact with a chemiluminescent
substrate, and photoelectrically detecting chemiluminescent
emission released from the labeling substance.
[0050] According to this preferred aspect of the present invention,
the substrate of the biochemical analysis unit is made of a
material capable of attenuating radiation energy and light energy,
and the biochemical analysis is effected based on biochemical
analysis data produced by the steps of preparing the biochemical
analysis unit by specifically binding a substance derived from a
living organism and labeled with, in addition to a radioactive
labeling substance, a fluorescent substance and a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate with the specific binding
substances, thereby selectively labeling the plurality of
absorptive regions, irradiating the biochemical analysis unit with
a stimulating ray to stimulate the fluorescent substance, and
photoelectrically detecting fluorescence released from the
fluorescent substance, while bringing the biochemical analysis unit
into contact with a chemiluminescent substrate, and
photoelectrically detecting chemiluminescent emission released from
the labeling substance. A specimen can therefore be labeled with a
fluorescent substance and a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate, in addition to a radioactive labeling
substance, and, therefore, the utility of biochemical analysis can
be improved.
[0051] The above and other objects of the present invention can be
also accomplished by a biochemical analyzing method comprising the
steps of preparing a biochemical analysis unit comprising an
absorptive substrate formed of an absorptive material and a
perforated plate made of a material capable of attenuating
radiation energy and light energy and formed with a plurality of
through-holes, the perforated plate being closely contacted with at
least one surface of the absorptive substrate to form a plurality
of absorptive regions of the absorptive substrate in the plurality
of through-holes formed in the perforated plate, the plurality of
absorptive regions being selectively labeled with a radioactive
labeling substance by spotting specific binding substances, which
can specifically bind with a substance derived from a living
organism and whose sequence, base length, composition and the like
are known, in the plurality of absorptive regions and specifically
binding a substance derived from a living organism and labeled with
a radioactive labeling substance, superposing the biochemical
analysis unit and a stimulable phosphor sheet in which a stimulable
phosphor layer is formed via the perforated plate so that the
stimulable phosphor layer faces the plurality of absorptive
regions, thereby exposing the stimulable phosphor layer to the
radioactive labeling substance contained in the plurality of
absorptive regions, irradiating the stimulable phosphor layer
exposed to the radioactive labeling substance with a stimulating
ray to excite stimulable phosphor contained in the stimulable
phosphor layer, photoelectrically detecting stimulated emission
released from the stimulable phosphor contained in the stimulable
phosphor layer to produce biochemical analysis data, and effecting
biochemical analysis based on the biochemical analysis data.
[0052] According to this aspect of the present invention, a
biochemical analyzing method comprises the steps of preparing a
biochemical analysis unit comprising an absorptive substrate formed
of an absorptive material and a perforated plate made of a material
capable of attenuating radiation energy and light energy and formed
with a plurality of through-holes, the perforated plate being
closely contacted with at least one surface of the absorptive
substrate so that a plurality of absorptive regions are formed of
the absorptive substrate in the plurality of the through-holes
formed in the perforated plate, the plurality of absorptive regions
being selectively labeled with a radioactive labeling substance by
spotting specific binding substances, which can specifically bind
with a substance derived from a living organism and whose sequence,
base length, composition and the like are known, in the plurality
of absorptive regions and specifically binding a substance derived
from a living organism and labeled with a radioactive labeling
substance, superposing the biochemical analysis unit and a
stimulable phosphor sheet in which a stimulable phosphor layer is
formed via the perforated plate so that the stimulable phosphor
layer faces the plurality of absorptive regions, thereby exposing
the stimulable phosphor layer to the radioactive labeling substance
contained in the plurality of absorptive regions, irradiating the
stimulable phosphor layer exposed to the radioactive labeling
substance with a stimulating ray to excite stimulable phosphor
contained in the stimulable phosphor layer, photoelectrically
detecting stimulated emission released from the stimulable phosphor
contained in the stimulable phosphor layer to produce biochemical
analysis data, and effecting biochemical analysis based on the
biochemical analysis data. Therefore, since electron beams (.beta.
rays) released from the radioactive labeling substance contained in
the individual absorptive regions and electron beams released from
neighboring absorptive regions can be reliably separated by the
perforated plate, thereby reliably preventing electron beams
released from the radioactive labeling substance contained in the
individual absorptive regions from advancing to regions of the
stimulable phosphor layer that should be exposed to electron beams
released from neighboring absorptive regions, it is possible to
efficiently prevent noise caused by the scattering of electron
beams released from the radioactive labeling substance from being
generated in biochemical analysis data produced by irradiating the
stimulable phosphor layer exposed to the radioactive labeling
substance with a stimulating ray and photoelectrically detecting
stimulated emission released from the stimulable phosphor layer and
produce biochemical analysis data having high quantitative
accuracy.
[0053] In a preferred aspect of the present invention, perforated
plates are closely contacted with both surfaces of the absorptive
substrate, thereby forming the biochemical analysis unit, and
biochemical analysis data are produced by superposing the
biochemical analysis unit and the stimulable phosphor sheet via one
of the perforated plates so that the stimulable phosphor layer
faces the plurality of absorptive regions and exposing the
stimulable phosphor layer to a radioactive labeling substance
contained in the plurality of absorptive regions.
[0054] In a preferred aspect of the present invention, the specific
binding substances are spotted through the plurality of
through-holes in the plurality of absorptive regions formed on the
absorptive substrate.
[0055] In a preferred aspect of the present invention, a plurality
of dot-like stimulable phosphor layer regions are formed
spaced-apart in the stimulable phosphor sheet in the same pattern
as that of the plurality of through-holes formed in the perforated
plate, and the biochemical analysis unit and the stimulable
phosphor sheet are superposed on each other so that each of the
plurality of dot-like stimulable phosphor layer regions faces one
of the plurality of absorptive regions via one of the through-holes
formed in the perforated plate, thereby exposing the plurality of
dot-like stimulable phosphor layer regions to a radioactive
labeling substance contained in the plurality of absorptive
regions.
[0056] According to this preferred aspect of the present invention,
a plurality of dot-like stimulable phosphor layer regions are
formed spaced-apart in the stimulable phosphor sheet in the same
pattern as that of the plurality of through-holes formed in the
perforated plate, and the biochemical analysis unit and the
stimulable phosphor sheet are superposed on each other so that each
of the plurality of dot-like stimulable phosphor layer regions
faces one of the plurality of absorptive regions via one of the
through-holes formed in the perforated plate, thereby exposing the
plurality of dot-like stimulable phosphor layer regions to a
radioactive labeling substance contained in the plurality of
absorptive regions. Electron beams (.beta. rays) released from a
radioactive labeling substance contained in the individual
absorptive regions are therefore prevented from being scattered in
the substrate and scattered electron beams are prevented from
advancing to the dot-like stimulable phosphor layer regions facing
neighboring absorptive regions. Therefore, the plurality of
dot-like stimulable phosphor layer regions formed in the stimulable
phosphor sheet can be reliably exposed to the radioactive labeling
substance contained in corresponding absorptive regions, thereby
improving the quantitative accuracy of biochemical analysis.
[0057] In a preferred aspect of the present invention, the
perforated plate is made of a material capable of attenuating
radiation energy and light energy, and the biochemical analysis is
effected based on biochemical analysis data produced by the steps
of preparing the biochemical analysis unit by specifically binding
a substance derived from a living organism and labeled with a
fluorescent substance, in addition to a radioactive labeling
substance, with the specific binding substances, thereby
selectively labeling the plurality of absorptive regions;
irradiating the biochemical analysis unit with a stimulating ray
through the plurality of the through-holes formed in the perforated
plate, thereby stimulating the fluorescent substance, and
photoelectrically detecting fluorescence released from the
fluorescent substance.
[0058] According to this preferred aspect of the present invention,
the perforated plate is made of a material capable of attenuating
radiation energy and light energy, and the biochemical analysis is
effected based on biochemical analysis data produced by the steps
of preparing the biochemical analysis unit by specifically binding
a substance derived from a living organism and labeled with a
fluorescent substance, in addition to a radioactive labeling
substance, with the specific binding substances, thereby
selectively labeling the plurality of absorptive regions,
irradiating the biochemical analysis unit with a stimulating ray
through the plurality of the through-holes formed in the perforated
plate, thereby stimulating the fluorescent substance, and
photoelectrically detecting fluorescence released from the
fluorescent substance. A specimen can therefore be labeled with a
fluorescent substance in addition to a radioactive labeling
substance and, therefore, the utility of biochemical analysis can
be improved.
[0059] In a preferred aspect of the present invention, the
perforated plate is made of a material capable of attenuating
radiation energy and light energy, and the biochemical analysis is
effected based on biochemical analysis data produced by the steps
of preparing the biochemical analysis unit by specifically binding
a substance derived from a living organism and labeled with, in
addition to a radioactive labeling substance, a labeling substance
which generates chemiluminescent emission when it contacts a
chemiluminescent substrate with the specific binding substances,
thereby selectively labeling the plurality of absorptive regions,
bringing the biochemical analysis unit into close contact with a
chemiluminescent substrate through the plurality of the
through-holes formed in the perforated plate, and photoelectrically
detecting chemiluminescent emission released from the labeling
substance.
[0060] According to this preferred aspect of the present invention,
the substrate of the biochemical analysis unit is made of a
material capable of attenuating radiation energy and light energy,
and the biochemical analysis is effected based on biochemical
analysis data produced by the steps of preparing the biochemical
analysis unit by specifically binding a substance derived from a
living organism and labeled with, in addition to a radioactive
labeling substance, a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate with the specific binding substances, thereby selectively
labeling the plurality of absorptive regions, bringing the
biochemical analysis unit into close contact with a
chemiluminescent substrate through the plurality of the
through-holes formed in the perforated plate, and photoelectrically
detecting chemiluminescent emission released from the labeling
substance. A specimen can therefore be labeled with a labeling
substance capable of generating chemiluminescent emission when it
contacts a chemiluminescent substrate, in addition to a radioactive
labeling substance, and, therefore, the utility of biochemical
analysis can be improved.
[0061] In a preferred aspect of the present invention, the
perforated plate is made of a material capable of attenuating
radiation energy and light energy, and the biochemical analysis is
effected based on biochemical analysis data produced by the steps
of preparing the biochemical analysis unit by specifically binding
a substance derived from a living organism and labeled with, in
addition to a radioactive labeling substance, a fluorescent
substance and a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate with the
specific binding substances, thereby selectively labeling the
plurality of absorptive regions, irradiating the biochemical
analysis unit with a stimulating ray through the plurality of the
through-holes formed in the perforated plate to stimulate the
fluorescent substance, and photoelectrically detecting fluorescence
released from the fluorescent substance, while bringing the
biochemical analysis unit into close contact with a
chemiluminescent substrate through the plurality of the
through-holes formed in the perforated plate, and photoelectrically
detecting chemiluminescent emission released from the labeling
substance.
[0062] According to this preferred aspect of the present invention,
the perforated plate is made of a material capable of attenuating
radiation energy and light energy, and the biochemical analysis is
effected based on biochemical analysis data produced by the steps
of preparing the biochemical analysis unit by specifically binding
a substance derived from a living organism and labeled with, in
addition to a radioactive labeling substance, a fluorescent
substance and a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate with the
specific binding substances, thereby selectively labeling the
plurality of absorptive regions, irradiating the biochemical
analysis unit with a stimulating ray through the plurality of the
through-holes formed in the perforated plate to stimulate the
fluorescent substance, and photoelectrically detecting fluorescence
released from the fluorescent substance, while bringing the
biochemical analysis unit into close contact with a
chemiluminescent substrate through the plurality of the
through-holes formed in the perforated plate, and photoelectrically
detecting chemiluminescent emission released from the labeling
substance. A specimen can therefore be labeled with a fluorescent
substance and a labeling substance capable of generating
chemiluminescent emission when it contacts a chemiluminescent
substrate, in addition to a radioactive labeling substance, and,
therefore, the utility of biochemical analysis can be improved.
[0063] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of preparing a biochemical analysis unit by spotting
specific binding substances, which can specifically bind with a
substance derived from a living organism and whose sequence, base
length, composition and the like are known, in a plurality of
absorptive regions formed in a plurality of holes formed in a
substrate made of a material capable of attenuating light energy
and specifically binding a substance derived from a living organism
and labeled with a fluorescent substance with the specific binding
substances, thereby selectively labeling a plurality of absorptive
regions, irradiating the biochemical analysis unit with a
stimulating ray, thereby exciting the fluorescent substance,
photoelectrically detecting fluorescence released from the
fluorescent substance, thereby producing biochemical analysis data,
and effecting biochemical analysis based on the biochemical
analysis data.
[0064] According to this aspect of the present invention, the
biochemical analysis unit is prepared by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions formed
in a plurality of holes formed in a substrate made of a material
capable of attenuating radiation energy and specifically binding a
substance derived from a living organism and labeled with a
fluorescent substance with the specific binding substances, thereby
selectively labeling a plurality of absorptive regions. Biochemical
analysis data are then produced by irradiating the biochemical
analysis unit with a stimulating ray to stimulate the fluorescent
substance and photoelectrically detecting fluorescence released
from the fluorescent substance and biochemical analysis is effected
based on the biochemical analysis data. Therefore, when the
biochemical data are produced by irradiating the biochemical
analysis unit with a stimulating ray and photoelectrically
detecting fluorescence released from the fluorescent substance,
since fluorescence is reliably prevented from being scattered in
the substrate of the biochemical analysis unit, it is possible to
efficiently prevent noise caused by the scattering of fluorescence
from being generated in biochemical analysis data produced by
photoelectrically detecting fluorescence and to effect biochemical
analysis with high quantitative accuracy.
[0065] In a preferred aspect of the present invention, the
plurality of absorptive regions are formed by charging an
absorptive material in the plurality of holes formed in the
substrate of the biochemical analysis unit.
[0066] In a preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as through-holes.
[0067] In another preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as recesses.
[0068] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of preparing a biochemical analysis unit by spotting
specific binding substances, which can specifically bind with a
substance derived from a living organism and whose sequence, base
length, composition and the like are known, in a plurality of
absorptive regions formed in a plurality of holes formed in a
substrate made of a material capable of attenuating light energy
and specifically binding a substance derived from a living organism
and labeled with a labeling substance capable of generating
chemiluminescent emission when it contacts a chemiluminescent
substrate with the specific binding substances, thereby selectively
labeling the plurality of absorptive regions, bringing the
biochemical analysis unit into close contact with a
chemiluminescent substrate, photoelectrically detecting
chemiluminescent emission released from the labeling substance,
thereby producing biochemical analysis data, and effecting
biochemical analysis based on the biochemical analysis data.
[0069] According to this aspect of the present invention, the
biochemical analysis unit is prepared by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions formed
in a plurality of holes formed in a substrate made of a material
capable of attenuating radiation energy and specifically binding a
substance derived from a living organism and labeled with a
labeling substance capable of generating chemiluminescent emission
when it contacts a chemiluminescent substrate with the specific
binding substances, thereby selectively labeling the plurality of
absorptive regions. Biochemical analysis data are the produced by
bringing the biochemical analysis unit into close contact with a
chemiluminescent substrate and photoelectrically detecting
chemiluminescent emission released from the labeling substance and
biochemical analysis is effected based on the biochemical analysis
data. Therefore, when the biochemical data are produced by bringing
the biochemical analysis unit into close contact with a
chemiluminescent substrate and photoelectrically detecting
chemiluminescent emission released from the labeling substance,
since chemiluminescent emission is reliably prevented from being
scattered in the substrate of the biochemical analysis unit, it is
possible to efficiently prevent noise caused by the scattering of
chemiluminescent emission from being generated in biochemical
analysis data produced by photoelectrically detecting
chemiluminescent emission and effect biochemical analysis with high
quantitative accuracy.
[0070] In a preferred aspect of the present invention, the
plurality of absorptive regions are formed by charging an
absorptive material in the plurality of holes formed in the
substrate of the biochemical analysis unit.
[0071] In a preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as through-holes.
[0072] In another preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as recesses.
[0073] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of preparing a biochemical analysis unit by spotting
specific binding substances, which can specifically bind with a
substance derived from a living organism and whose sequence, base
length, composition and the like are known, in a plurality of
absorptive regions formed in a plurality of holes formed in a
substrate made of a material capable of attenuating light energy
and specifically binding a substance derived from a living organism
and labeled with a fluorescent substance and a labeling substance
capable of generating chemiluminescent emission when it contacts a
chemiluminescent substrate with the specific binding substances,
thereby selectively labeling the plurality of absorptive regions,
irradiating the biochemical analysis unit with a stimulating ray to
excite the fluorescent substance, and photoelectrically detecting
fluorescence released from the fluorescent substance, thereby
producing biochemical analysis data, while bringing the biochemical
analysis unit into close contact with a chemiluminescent substrate,
photoelectrically detecting chemiluminescent emission released from
the labeling substance, thereby producing biochemical analysis
data, and effecting biochemical analysis based on the biochemical
analysis data.
[0074] According to this aspect of the present invention, the
biochemical analysis unit is prepared by spotting specific binding
substances, which can specifically bind with a substance derived
from a living organism and whose sequence, base length, composition
and the like are known, in a plurality of absorptive regions formed
in a plurality of holes formed in a substrate made of a material
capable of attenuating radiation energy and specifically binding a
substance derived from a living organism and labeled with a
fluorescent substance and a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate with the specific binding substances,
thereby selectively labeling the plurality of absorptive regions.
Biochemical analysis data are then produced by irradiating the
biochemical analysis unit with a stimulating ray to stimulate the
fluorescent substance and photoelectrically detecting fluorescence
released from the fluorescent substance and are also produced by
bringing the biochemical analysis unit into close contact with a
chemiluminescent substrate and photoelectrically detecting
chemiluminescent emission released from the labeling substance, and
biochemical analysis is effected based on the biochemical analysis
data. Therefore, when the biochemical data are produced by reading
fluorescent data, since fluorescence is reliably prevented from
being scattered in the substrate of the biochemical analysis unit,
it is possible to efficiently prevent noise caused by the
scattering of fluorescence from being generated in biochemical
analysis data produced by photoelectrically detecting fluorescence.
On the other hand, when the biochemical data are produced by
reading chemiluminescent data, since chemiluminescent emission is
reliably prevented from being scattered in the substrate of the
biochemical analysis unit, it is possible to efficiently prevent
noise caused by the scattering of chemiluminescent emission from
being generated in biochemical analysis data produced by
photoelectrically detecting chemiluminescent emission. Therefore,
biochemical analysis can be effected with high quantitative
accuracy.
[0075] In a preferred aspect of the present invention, the
plurality of absorptive regions are formed by charging an
absorptive material in the plurality of holes formed in the
substrate of the biochemical analysis unit.
[0076] In a preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as through-holes.
[0077] In another preferred aspect of the present invention, the
plurality of holes formed in the substrate of the biochemical
analysis unit are constituted as recesses.
[0078] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of bringing an absorptive substrate made of an absorptive
material and formed with a plurality of absorptive regions by
spotting thereon specific binding substances, which can
specifically bind with a substance derived from a living organism
and whose sequence, base length, composition and the like are
known, the plurality of the absorptive regions being selectively
labeled by specifically binding a substance derived from a living
organism and labeled with a fluorescent substance with the specific
binding substances contained in the plurality of absorptive
regions, into close contact with a perforated plate made of a
material capable of attenuating light energy and formed with a
plurality of through-holes at positions corresponding to the
plurality of absorptive regions formed in the absorptive substrate,
irradiating the plurality of absorptive regions formed in the
absorptive substrate through the plurality of through-holes formed
in the perforated plate to stimulate the fluorescent substance,
photoelectrically detecting fluorescence released from the
fluorescent substance, thereby producing biochemical analysis data,
and effecting biochemical analysis based on the biochemical
analysis data.
[0079] According to this aspect of the present invention, a
biochemical analyzing method comprises the steps of bringing an
absorptive substrate made of an absorptive material and formed with
a plurality of absorptive regions by spotting thereon specific
binding substances, which can specifically bind with a substance
derived from a living organism and whose sequence, base length,
composition and the like are known, onto the absorptive substrate,
the plurality of the absorptive regions being selectively labeled
by specifically binding a substance derived from a living organism
and labeled with a fluorescent substance with the specific binding
substances contained in the plurality of absorptive regions, into
close contact with a perforated plate made of a material capable of
attenuating light energy and formed with a plurality of
through-holes at positions corresponding to the plurality of
absorptive regions formed in the absorptive substrate, irradiating
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate to stimulate the fluorescent substance,
photoelectrically detecting fluorescence released from the
fluorescent substance, thereby producing biochemical analysis data,
and effecting biochemical analysis based on the biochemical
analysis data. Therefore, when biochemical analysis data are
produced by irradiating the plurality of absorptive regions formed
in the absorptive substrate with a stimulating ray through the
plurality of through-holes formed in the perforated plate and
photoelectrically detecting fluorescence released from the
fluorescent substance, since fluorescence released from each of the
plurality of absorptive regions can be reliably separated by the
perforated plate from fluorescence released from neighboring
absorptive regions, it is possible to efficiently prevent noise
caused by the scattering of fluorescence from being generated in
biochemical analysis data produced by photoelectrically detecting
fluorescence and effect biochemical analysis with high quantitative
accuracy.
[0080] In a preferred aspect of the present invention, the
biochemical analysis unit is prepared by bringing perforated plates
into close contact with both surfaces of the absorptive substrate
and biochemical data are produced by irradiating the plurality of
absorptive regions formed in the absorptive substrate with a
stimulating ray through the plurality of through-holes formed in
one of the perforated plates to stimulate a fluorescent substance
and photoelectrically detecting fluorescence released from the
fluorescent substance.
[0081] In a preferred aspect of the present invention, the specific
binding substances are spotted through the plurality of
through-holes formed in the perforated plate in the plurality of
absorptive regions formed in the absorptive substrate.
[0082] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of bringing an absorptive substrate made of an absorptive
material and formed with a plurality of absorptive regions by
spotting thereon specific binding substances, which can
specifically bind with a substance derived from a living organism
and whose sequence, base length, composition and the like are
known, the plurality of the absorptive regions being selectively
labeled by specifically binding a substance derived from a living
organism and labeled with a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate with the specific binding substances
contained in the plurality of absorptive regions, into close
contact with a perforated plate made of a material capable of
attenuating light energy and formed with a plurality of
through-holes at positions corresponding to the plurality of
absorptive regions formed in the absorptive substrate, bringing a
chemiluminescent substrate into close contact with the plurality of
absorptive regions formed in the absorptive substrate through the
plurality of through-holes formed in the perforated plate,
photoelectrically detecting chemiluminescent emission released from
the labeling substance, thereby producing biochemical analysis
data, and effecting biochemical analysis based on the biochemical
analysis data.
[0083] According to this aspect of the present invention, a
biochemical analyzing method comprises the steps of bringing an
absorptive substrate made of an absorptive material and formed with
a plurality of absorptive regions by spotting thereon specific
binding substances, which can specifically bind with a substance
derived from a living organism and whose sequence, base length,
composition and the like are known, onto the absorptive substrate,
the plurality of the absorptive regions being selectively labeled
by specifically binding a substance derived from a living organism
and labeled with a labeling substance capable of generating
chemiluminescent emission when it contacts a chemiluminescent
substrate with the specific binding substances contained in the
plurality of absorptive regions, into close contact with a
perforated plate made of a material capable of attenuating light
energy and formed with a plurality of through-holes at positions
corresponding to the plurality of absorptive regions formed in the
absorptive substrate, bringing a chemiluminescent substrate into
close contact with the plurality of absorptive regions formed in
the absorptive substrate through the plurality of through-holes
formed in the perforated plate, photoelectrically detecting
chemiluminescent emission released from the labeling substance,
thereby producing biochemical analysis data, and effecting
biochemical analysis based on the biochemical analysis data.
Therefore, when biochemical analysis data are produced by bringing
a chemiluminescent substrate into close contact with the plurality
of absorptive regions formed in the absorptive substrate through
the plurality of through-holes formed in the perforated plate and
photoelectrically detecting chemiluminescent emission released from
the labeling substance, since chemiluminescent emission released
from each of the plurality of absorptive regions can be reliably
separated by the perforated plate from chemiluminescent emission
released from neighboring absorptive regions, it is possible to
efficiently prevent noise caused by the scattering of
chemiluminescent emission from being generated in biochemical
analysis data produced by photoelectrically detecting
chemiluminescent emission and effect biochemical analysis with high
quantitative accuracy.
[0084] In a preferred aspect of the present invention, the
biochemical analysis unit is prepared by bringing perforated plates
into close contact with the both surfaces of the absorptive
substrate and biochemical data are produced by bringing a
chemiluminescent substrate into close contact with the plurality of
absorptive regions formed in the absorptive substrate through the
plurality of through-holes formed in one of the perforated plates
and photoelectrically detecting chemiluminescent emission released
from the labeling substance.
[0085] In a preferred aspect of the present invention, the specific
binding substances are spotted through the plurality of
through-holes formed in the perforated plate in the plurality of
absorptive regions formed in the absorptive substrate.
[0086] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of bringing an absorptive substrate made of an absorptive
material and formed with a plurality of absorptive regions by
spotting thereon specific binding substances, which can
specifically bind with a substance derived from a living organism
and whose sequence, base length, composition and the like are
known, the plurality of the absorptive regions being selectively
labeled by specifically binding a substance derived from a living
organism and labeled with a fluorescent substance and a labeling
substance capable of generating chemiluminescent emission when it
contacts a chemiluminescent substrate with the specific binding
substances contained in the plurality of absorptive regions, into
close contact with a perforated plate made of a material capable of
attenuating light energy and formed with a plurality of
through-holes at positions corresponding to the plurality of
absorptive regions formed in the absorptive substrate, irradiating
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate to stimulate the fluorescent substance, and
photoelectrically detecting fluorescence released from the
fluorescent substance, thereby producing biochemical analysis data,
while bringing a chemiluminescent substrate into close contact with
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate, and photoelectrically detecting chemiluminescent
emission released from the labeling substance, thereby producing
biochemical analysis data, and effecting biochemical analysis based
on the biochemical analysis data.
[0087] According to this aspect the present invention, a
biochemical analyzing method comprises the steps of bringing an
absorptive substrate made of an absorptive material and formed with
a plurality of absorptive regions by spotting thereon specific
binding substances, which can specifically bind with a substance
derived from a living organism and whose sequence, base length,
composition and the like are known, the plurality of the absorptive
regions being selectively labeled by specifically binding a
substance derived from a living organism and labeled with a
fluorescent substance and a labeling substance capable of
generating chemiluminescent emission when it contacts a
chemiluminescent substrate with the specific binding substances
contained in the plurality of absorptive regions, into close
contact with a perforated plate made of a material capable of
attenuating light energy and formed with a plurality of
through-holes at positions corresponding to the plurality of
absorptive regions formed in the absorptive substrate, irradiating
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate to stimulate the fluorescent substance, and
photoelectrically detecting fluorescence released from the
fluorescent substance, thereby producing biochemical analysis data,
while bringing a chemiluminescent substrate into close contact with
the plurality of absorptive regions formed in the absorptive
substrate through the plurality of through-holes formed in the
perforated plate, and photoelectrically detecting chemiluminescent
emission released from the labeling substance, thereby producing
biochemical analysis data, and effecting biochemical analysis based
on the biochemical analysis data. Therefore, when biochemical
analysis data are produced by irradiating the plurality of
absorptive regions formed in the absorptive substrate with a
stimulating ray through the plurality of through-holes formed in
the perforated plate and photoelectrically detecting fluorescence
released from the fluorescent substance, since fluorescence
released from each of the plurality of absorptive regions can be
reliably separated by the perforated plate from fluorescence
released from neighboring absorptive regions, it is possible to
efficiently prevent noise caused by the scattering of fluorescence
from being generated in biochemical analysis data produced by
photoelectrically detecting fluorescence. On the other hand, when
biochemical analysis data are produced by bringing a
chemiluminescent substrate into close contact with the plurality of
absorptive regions formed in the absorptive substrate through the
plurality of through-holes formed in the perforated plate and
photoelectrically detecting chemiluminescent emission released from
the labeling substance, since chemiluminescent emission released
from each of the plurality of absorptive regions can be reliably
separated by the perforated plate from chemiluminescent emission
released from neighboring absorptive regions, it is possible to
efficiently prevent noise caused by the scattering of
chemiluminescent emission from being generated in biochemical
analysis data produced by photoelectrically detecting
chemiluminescent emission. Therefore, biochemical analysis can be
effected with high quantitative accuracy.
[0088] In a preferred aspect of the present invention, the
biochemical analysis unit is prepared by bringing perforated plates
into close contact with the both surfaces of the absorptive
substrate and biochemical data are produced by irradiating the
plurality of absorptive regions formed in the absorptive substrate
with a stimulating ray through the plurality of through-holes
formed in one of the perforated plates to stimulate a fluorescent
substance and photoelectrically detecting fluorescence released
from the fluorescent substance and are also produced by bringing a
chemiluminescent substrate into close contact with the plurality of
absorptive regions formed in the absorptive substrate through the
plurality of through-holes formed in one of the perforated plates
and photoelectrically detecting chemiluminescent emission released
from the labeling substance.
[0089] In a preferred aspect of the present invention, the specific
binding substances are spotted through the plurality of
through-holes formed in the perforated plate in the plurality of
absorptive regions formed in the absorptive substrate.
[0090] In a preferred aspect of the present invention, the
substance derived from a living organism is specifically bound with
specific binding substances by a reaction selected from a group
consisting of hybridization, antigen-antibody reaction and
receptor-ligand reaction.
[0091] In a preferred aspect of the present invention, the material
capable of attenuating radiation energy has a property of reducing
the energy of radiation to 1/5 or less when the radiation travels
in the material by a distance equal to that between neighboring
absorptive regions.
[0092] In a further preferred aspect of the present invention, a
material capable of attenuating radiation energy has a property of
reducing the energy of radiation to {fraction (1/10)} or less when
the radiation travels in the material by a distance equal to that
between neighboring absorptive regions.
[0093] In a further preferred aspect of the present invention, a
material capable of attenuating radiation energy has a property of
reducing the energy of radiation to {fraction (1/50)} or less when
the radiation travels in the material by a distance equal to that
between neighboring absorptive regions.
[0094] In a further preferred aspect of the present invention, a
material capable of attenuating radiation energy has a property of
reducing the energy of radiation to {fraction (1/100)} or less when
the radiation travels in the material by a distance equal to that
between neighboring absorptive regions.
[0095] In a further preferred aspect of the present invention, a
material capable of attenuating radiation energy has property of
reducing the energy of radiation to {fraction (1/500)} or less when
the radiation travels in the material by a distance equal to that
between neighboring absorptive regions.
[0096] In a further preferred aspect of the present invention, a
material capable of attenuating radiation energy has a property of
reducing the energy of radiation to {fraction (1/1000)} or less
when the radiation travels in the material by a distance equal to
that between neighboring absorptive regions.
[0097] In a preferred aspect of the present invention, a material
capable of attenuating light energy has a property of reducing the
energy of light to 1/5 or less when the light travels in the
material by a distance equal to that between neighboring absorptive
regions.
[0098] In a further preferred aspect of the present invention, a
material capable of attenuating light energy has a property of
reducing the energy of light to {fraction (1/10)} or less when the
light travels in the material by a distance equal to that between
neighboring absorptive regions.
[0099] In a further preferred aspect of the present invention, a
material capable of attenuating light energy has a property of
reducing the energy of light to {fraction (1/50)} or less when the
light travels in the material by a distance equal to that between
neighboring absorptive regions.
[0100] In a further preferred aspect of the present invention, a
material capable of attenuating light energy has a property of
reducing the energy of light to {fraction (1/100)} or less when the
light travels in the material by a distance equal to that between
neighboring absorptive regions.
[0101] In a further preferred aspect of the present invention, a
material capable of attenuating light energy has a property of
reducing the energy of light to {fraction (1/500)} or less when the
light travels in the material by a distance equal to that between
neighboring absorptive regions.
[0102] In a further preferred aspect of the present invention, a
material capable of attenuating light energy has a property of
reducing the energy of light to {fraction (1/1000)} or less when
the light travels in the material by a distance equal to that
between neighboring absorptive regions.
[0103] In the present invention, the material for forming the
substrate or the perforated plate of the biochemical analysis unit
is not particularly limited but may be of any type of inorganic
compound material or organic compound material insofar as it can
attenuate radiation energy and/or light energy. It is preferably
formed of metal material, ceramic material or plastic material.
[0104] In the present invention, illustrative examples of inorganic
compound materials capable of attenuating radiation energy and
preferably usable for forming a substrate or a perforated plate of
a biochemical analysis unit in the present invention include metals
such as gold, silver, copper, zinc, aluminum, titanium, tantalum,
chromium, iron, nickel, cobalt, lead, tin, selenium and the like;
alloys such as brass, stainless steel, bronze and the like; silicon
materials such as silicon, amorphous silicon, glass, quartz,
silicon carbide, silicon nitride and the like; metal oxides such as
aluminum oxide, magnesium oxide, zirconium oxide and the like; and
inorganic salts such as tungsten carbide, calcium carbide, calcium
sulfate, hydroxy apatite, gallium arsenide and the like. These may
have either a monocrystal structure or a polycrystal sintered
structure such as amorphous, ceramic or the like.
[0105] In the present invention, a high molecular compound is
preferably used as an organic compound material capable of
attenuating radiation energy. Illustrative examples of high
molecular compounds preferably usable for forming the substrate or
the perforated plate of the biochemical analysis unit in the
present invention include polyolefins such as polyethylene,
polypropylene and the like; acrylic resins such as polymethyl
methacrylate, polybutylacrylate/polymethyl methacrylate copolymer
and the like; polyacrylonitrile; polyvinyl chloride; polyvinylidene
chloride; polyvinylidene fluoride; polytetrafluoroethylene- ;
polychlorotrifuluoroethylene; polycarbonate; polyesters such as
polyethylene naphthalate, polyethylene terephthalate and the like;
nylons such as nylon-6, nylon-6, 6, nylon-4, 10 and the like;
polyimide; polysulfone; polyphenylene sulfide; silicon resins such
as polydiphenyl siloxane and the like; phenol resins such as
novolac and the like; epoxy resin; polyurethane; polystyrene,
butadiene-styrene copolymer; polysaccharides such as cellulose,
acetyl cellulose, nitrocellulose, starch, calcium alginate,
hydroxypropyl methyl cellulose and the like; chitin; chitosan;
urushi (Japanese lacquer); polyamides such as gelatin, collagen,
keratin and the like; and copolymers of these high molecular
materials. These may be a composite compound, and metal oxide
particles, glass fiber or the like may be added thereto as occasion
demands. Further, an organic compound material may be blended
therewith.
[0106] Since the capability of attenuating radiation energy
generally increases as specific gravity increases, in the case
where the substrate or the perforated plate of the biochemical
analysis unit is made of a material capable of attenuating
radiation energy in accordance with the present invention, the
substrate or the perforated plate of the biochemical analysis unit
is preferably formed of a compound material or a composite material
having specific gravity of 1.0 g/cm.sup.3 or more and more
preferably formed of a compound material or a composite material
having specific gravity of 1.5 g/cm.sup.3 to 23 g/cm.sup.3.
[0107] In the present invention, illustrative examples of inorganic
compound material capable of attenuating light energy and
preferably usable for forming the substrate or the perforated plate
of the biochemical analysis unit in the present invention include
metals such as gold, silver, copper, zinc, aluminum, titanium,
tantalum, chromium, iron, nickel, cobalt, lead, tin, selenium and
the like; alloys such as brass, stainless steel, bronze and the
like; silicon materials such as silicon, amorphous silicon, glass,
quartz, silicon carbide, silicon nitride and the like; metal oxides
such as aluminum oxide, magnesium oxide, zirconium oxide and the
like; and inorganic salts such as tungsten carbide, calcium
carbide, calcium sulfate, hydroxy apatite, gallium arsenide and the
like. These may have either a monocrystal structure or a
polycrystal sintered structure such as amorphous, ceramic or the
like.
[0108] In the present invention, a high molecular compound is
preferably used as an organic compound material capable of
attenuating light energy. Illustrative examples of high molecular
compounds preferably usable for forming a substrate or a perforated
plate of a biochemical analysis unit in the present invention
include polyolefins such as polyethylene, polypropylene and the
like; acrylic resins such as polymethyl methacrylate,
polybutylacrylate/polymethyl methacrylate copolymer and the like;
polyacrylonitrile; polyvinyl chloride; polyvinylidene chloride;
polyvinylidene fluoride; polytetrafluoroethylene;
polychlorotrifuluoroeth- ylene; polycarbonate; polyesters such as
polyethylene naphthalate, polyethylene terephthalate and the like;
nylons such as nylon-6, nylon-6, 6, nylon-4, 10 and the like;
polyimide; polysulfone; polyphenylene sulfide; silicon resins such
as polydiphenyl siloxane and the like; phenol resins such as
novolac and the like; epoxy resin; polyurethane; polystyrene,
butadiene-styrene copolymer; polysaccharides such as cellulose,
acetyl cellulose, nitrocellulose, starch, calcium alginate,
hydroxypropyl methyl cellulose and the like; chitin; chitosan;
urushi (Japanese lacquer); polyamides such as gelatin, collagen,
keratin and the like; and copolymers of these high molecular
materials. These may be a composite compound, and metal oxide
particles, glass fiber or the like may be added thereto as occasion
demands. Further, an organic compound material may be blended
therewith.
[0109] Since the capability of attenuating light energy generally
increases as scattering and/or absorption of light increases, in
the case where the substrate or the perforated plate of the
biochemical analysis unit is made of a material capable of
attenuating light energy, in the present invention, the substrate
or the perforated plate of the biochemical analysis unit preferably
has absorbance of 0.3 per cm (thickness) or more and more
preferably has absorbance of 1 per cm (thickness) or more. The
absorbance can be determined by placing an integrating sphere
immediately behind a plate-like member having a thickness of T cm,
measuring an amount A of transmitted light at a wavelength of probe
light or emission light used for measurement by a
spectrophotometer, and calculating A/T.
[0110] In the present invention, a light scattering substance or a
light absorbing substance may be added to the substrate or the
perforated plate of the biochemical analysis unit in order to
improve the capability of attenuating light energy. Particles of a
material different from a material forming the substrate or the
perforated plate of the biochemical analysis unit may be preferably
used as a light scattering substance and a pigment or dye may be
preferably used as a light absorbing substance.
[0111] In a preferred aspect of the present invention, the
substrate of the biochemical analysis unit is formed of a flexible
material.
[0112] According to this preferred aspect of the present invention,
since the substrate of the biochemical analysis unit is formed of a
flexible material, the biochemical analysis unit can be bent and be
brought into contact with a hybridization solution, thereby
hybridizing specific binding substances with a substance derived
from a living organism. Therefore, specific binding substances and
a substance derived from a living organism can be hybridized with
each other in a desired manner using a small amount of a
hybridization solution.
[0113] In a preferred aspect of the present invention, the
plurality of holes are regularly formed in the substrate of the
biochemical analysis unit.
[0114] In a preferred aspect of the present invention, a plurality
of holes having a substantially circular shape are formed in the
substrate of the biochemical analysis unit.
[0115] In another preferred aspect of the present invention, a
plurality of holes having a substantially rectangular shape are
formed in the substrate of the biochemical analysis unit.
[0116] In a preferred aspect of the present invention, the
substrate of the biochemical analysis unit is formed with 10 or
more holes.
[0117] In a further preferred aspect of the present invention, the
substrate of the biochemical analysis unit is formed with 50 or
more holes.
[0118] In a further preferred aspect of the present invention, the
substrate of the biochemical analysis unit is formed with 100 or
more holes.
[0119] In a further preferred aspect of the present invention, the
substrate of the biochemical analysis unit is formed with 1,000 or
more holes.
[0120] In a further preferred aspect of the present invention, the
substrate of the biochemical analysis unit is formed with 10,000 or
more holes.
[0121] In a further preferred aspect of the present invention, the
substrate of the biochemical analysis unit is formed with 100,000
or more holes.
[0122] In a preferred aspect of the present invention, each of the
plurality of holes formed in the substrate of the biochemical
analysis unit has a size of less than 5 mm.sup.2.
[0123] In a further preferred aspect of the present invention, each
of the plurality of holes formed in the substrate of the
biochemical analysis unit has a size of less than 1 mm.sup.2.
[0124] In a further preferred aspect of the present invention, each
of the plurality of holes formed in the substrate of the
biochemical analysis unit has a size of less than 0.5 mm.sup.2.
[0125] In a further preferred aspect of the present invention, each
of the plurality of holes formed in the substrate of the
biochemical analysis unit has a size of less than 0.1 mm.sup.2.
[0126] In a further preferred aspect of the present invention, each
of the plurality of holes formed in the substrate of the
biochemical analysis unit has a size of less than 0.05
mm.sup.2.
[0127] In a further preferred aspect of the present invention, each
of the plurality of holes formed in the substrate of the
biochemical analysis unit has a size of less than 0.01
mm.sup.2.
[0128] In the present invention, the density of the holes formed in
the substrate of the biochemical analysis unit is determined
depending upon the material of the substrate, the thickness of the
substrate, the kind of electron beam released from a radioactive
substance, the wavelength of fluorescence released from a
fluorescent substance or the like.
[0129] In a preferred aspect of the present invention, the
plurality of holes are formed in the substrate of the biochemical
analysis unit at a density of 10 or more per cm.sup.2.
[0130] In a further preferred aspect of the present invention, the
plurality of holes are formed in the substrate of the biochemical
analysis unit at a density of 50 or more per cm.sup.2.
[0131] In a further preferred aspect of the present invention, the
plurality of holes are formed in the substrate of the biochemical
analysis unit at a density of 100 or more per cm.sup.2.
[0132] In a further preferred aspect of the present invention, the
plurality of holes are formed in the substrate of the biochemical
analysis unit at a density of 500 or more per cm.sup.2.
[0133] In a further preferred aspect of the present invention, the
plurality of holes are formed in the substrate of the biochemical
analysis unit at a density of 1,000 or more per cm.sup.2.
[0134] In a further preferred aspect of the present invention, the
plurality of holes are formed in the substrate of the biochemical
analysis unit at a density of 5,000 or more per cm.sup.2.
[0135] In a further preferred aspect of the present invention, the
plurality of holes are formed in the substrate of the biochemical
analysis unit at a density of 10,000 or more per cm.sup.2.
[0136] In a preferred aspect of the present invention, a plurality
of through-holes are regularly formed in the perforated plate of
the biochemical analysis unit.
[0137] In a preferred aspect of the present invention, a plurality
of through-holes having a substantially circular shape are formed
in the perforated plate of the biochemical analysis unit.
[0138] In another preferred aspect of the present invention, a
plurality of through-holes having a substantially rectangular shape
are formed in the perforated plate of the biochemical analysis
unit.
[0139] In a preferred aspect of the present invention, the
perforated plate of the biochemical analysis unit is formed with 10
or more through-holes.
[0140] In a further preferred aspect of the present invention, the
perforated plate of the biochemical analysis unit is formed with 50
or more through-holes.
[0141] In a further preferred aspect of the present invention, the
perforated plate of the biochemical analysis unit is formed with
100 or more through-holes.
[0142] In a further preferred aspect of the present invention, the
perforated plate of the biochemical analysis unit is formed with
1,000 or more through-holes.
[0143] In a further preferred aspect of the present invention, the
perforated plate of the biochemical analysis unit is formed with
10,000 or more through-holes.
[0144] In a further preferred aspect of the present invention, the
perforated plate of the biochemical analysis unit is formed with
100,000 or more through-holes.
[0145] In a preferred aspect of the present invention, each of the
plurality of through-holes formed in the perforated plate of the
biochemical analysis unit has a size of less than 5 mm.sup.2.
[0146] In a further preferred aspect of the present invention, each
of the plurality of through-holes formed in the perforated plate of
the biochemical analysis unit has a size of less than 1
mm.sup.2.
[0147] In a further preferred aspect of the present invention, each
of the plurality of through-holes formed in the perforated plate of
the biochemical analysis unit has a size of less than 0.5
mm.sup.2.
[0148] In a further preferred aspect of the present invention, each
of the plurality of through-holes formed in the perforated plate of
the biochemical analysis unit has a size of less than 0.1
mm.sup.2.
[0149] In a further preferred aspect of the present invention, each
of the plurality of through-holes formed in the perforated plate of
the biochemical analysis unit has a size of less than 0.05
mm.sup.2.
[0150] In a further preferred aspect of the present invention, each
of the plurality of through-holes formed in the perforated plate of
the biochemical analysis unit has a size of less than 0.01
mm.sup.2.
[0151] In the present invention, the density of the through-holes
formed in the perforated plate of the biochemical analysis unit can
be arbitrarily determined depending upon the material of the
perforated plate, the thickness of the perforated plate and the
kind of electron beam released from the radioactive labeling
substance or the wavelength of fluorescence released from the
fluorescent substance and the like.
[0152] In a preferred aspect of the present invention, the
plurality of through-holes are formed in the perforated plate of
the biochemical analysis unit at a density of 10 or more per
cm.sup.2.
[0153] In a further preferred aspect of the present invention, the
plurality of through-holes are formed in the perforated plate of
the biochemical analysis unit at a density of 50 or more per
cm.sup.2.
[0154] In a further preferred aspect of the present invention, the
plurality of through-holes are formed in the perforated plate of
the biochemical analysis unit at a density of 100 or more per
cm.sup.2.
[0155] In a further preferred aspect of the present invention, the
plurality of through-holes are formed in the perforated plate of
the biochemical analysis unit at a density of 500 or more per
cm.sup.2.
[0156] In a further preferred aspect of the present invention, the
plurality of through-holes are formed in the perforated plate of
the biochemical analysis unit at a density of 1,000 or more per
cm.sup.2.
[0157] In a further preferred aspect of the present invention, the
plurality of through-holes are formed in the perforated plate of
the biochemical analysis unit at a density of 5,000 or more per
cm.sup.2.
[0158] In a further preferred aspect of the present invention, the
plurality of through-holes are formed in the perforated plate of
the biochemical analysis unit at a density of 10,000 or more per
cm.sup.2.
[0159] In the present invention, a porous material or a fiber
material may be preferably used as the absorptive material for
forming the absorptive region. The absorptive region may be formed
by combining a porous material and a fiber material.
[0160] In the present invention, a porous material for forming the
absorptive region may be any type of an organic material or an
inorganic material and may be an organic/inorganic composite
material.
[0161] In the present invention, an organic porous material used
for forming the absorptive region is not particularly limited but a
carbon porous material such as an activated carbon or a porous
material capable of forming a membrane filter is preferably used.
Illustrative examples of porous materials capable of forming a
membrane filter include nylons such as nylon-6, nylon-6, 6,
nylon-4, 10; cellulose derivatives such as nitrocellulose, acetyl
cellulose, butyric-acetyl cellulose; collagen; alginic acids such
as alginic acid, calcium alginate, alginic acid/poly-L-lysine
polyionic complex; polyolefins such as polyethylene, polypropylene;
polyvinyl chloride; polyvinylidene chloride; polyfluoride such as
polyvinylidene fluoride, polytetrafluoride; and copolymers or
composite materials thereof.
[0162] In the present invention, an inorganic porous material used
for forming the absorptive region is not particularly limited.
Illustrative examples of inorganic porous materials preferably
usable in the present invention include metals such as platinum,
gold, iron, silver, nickel, aluminum and the like; metal oxides
such as alumina, silica, titania, zeolite and the like; metal salts
such as hydroxy apatite, calcium sulfate and the like; and
composite materials thereof.
[0163] In the present invention, a fiber material used for forming
the absorptive region is not particularly limited. Illustrative
examples of fiber materials preferably usable in the present
invention include nylons such as nylon-6, nylon-6, 6, nylon-4, 10;
and cellulose derivatives such as nitrocellulose, acetyl cellulose,
butyric-acetyl cellulose.
[0164] In the present invention, in the case where a plurality of
dot-like stimulable phosphor layer regions are formed in the
support of the stimulable phosphor sheet, the plurality of dot-like
stimulable phosphor layer regions may be formed on the surface of
the support or the plurality of dot-like stimulable phosphor layer
regions may be formed in a plurality of holes formed dot-like in
the support.
[0165] In the present invention, in the case where a plurality of
dot-like stimulable phosphor layer regions are formed in the
support of the stimulable phosphor sheet, the plurality of dot-like
stimulable phosphor layer regions are formed in the same pattern as
that of the absorptive regions formed in the biochemical analysis
unit.
[0166] In a preferred aspect of the present invention, a plurality
of through-holes are formed dot-like in the support of the
stimulable phosphor sheet and stimulable phosphor layer regions are
formed in the plurality of through-holes.
[0167] In a further preferred aspect of the present invention,
stimulable phosphor layer regions are formed by charging stimulable
phosphor in the plurality of through-holes.
[0168] In another preferred aspect of the present invention, a
plurality of recesses are dot-like formed in the support of the
stimulable phosphor sheet and stimulable phosphor layer regions are
formed in the plurality of recesses.
[0169] In a further preferred aspect of the present invention,
stimulable phosphor layer regions are formed by charging stimulable
phosphor in the plurality of recesses.
[0170] In a preferred aspect of the present invention, a plurality
of dot-like stimulable phosphor layer regions are regularly formed
in the stimulable phosphor sheet.
[0171] In the present invention, in the case where a plurality of
dot-like stimulable phosphor layer regions are formed in the
support of the stimulable phosphor sheet, the material for forming
the support of the stimulable phosphor sheet preferably has a
property of attenuating radiation energy. The material capable of
attenuating radiation energy and usable for forming the support of
the stimulable phosphor sheet is not particularly limited but may
be of any type of inorganic compound material or organic compound
material insofar as it can attenuate radiation energy. It is
preferably formed of metal material, ceramic material or plastic
material.
[0172] In the present invention, illustrative examples of inorganic
compound materials capable of attenuating radiation energy and
preferably usable for forming the support of the stimulable
phosphor sheet in the present invention include metals such as
gold, silver, copper, zinc, aluminum, titanium, tantalum, chromium,
iron, nickel, cobalt, lead, tin, selenium and the like; alloys such
as brass, stainless steel, bronze and the like; silicon materials
such as silicon, amorphous silicon, glass, quartz, silicon carbide,
silicon nitride and the like; metal oxides such as aluminum oxide,
magnesium oxide, zirconium oxide and the like; and inorganic salts
such as tungsten carbide, calcium carbide, calcium sulfate, hydroxy
apatite, gallium arsenide and the like. These may have either a
monocrystal structure or a polycrystal sintered structure such as
amorphous, ceramic or the like.
[0173] In the present invention, a high molecular compound is
preferably used as an organic compound material capable of
attenuating radiation energy. Illustrative examples of high
molecular compounds and preferably usable for forming a support of
the stimulable phosphor sheet in the present invention include
polyolefins such as polyethylene, polypropylene and the like;
acrylic resins such as polymethyl methacrylate,
polybutylacrylate/polymethyl methacrylate copolymer and the like;
polyacrylonitrile; polyvinyl chloride; polyvinylidene chloride;
polyvinylidene fluoride; polytetrafluoroethylene;
polychlorotrifuluoroeth- ylene; polycarbonate; polyesters such as
polyethylene naphthalate, polyethylene terephthalate and the like;
nylons such as nylon-6, nylon-6, 6, nylon-4, 10 and the like;
polyimide; polysulfone; polyphenylene sulfide; silicon resins such
as polydiphenyl siloxane and the like; phenol resins such as
novolac and the like; epoxy resin; polyurethane; polystyrene,
butadiene-styrene copolymer; polysaccharides such as cellulose,
acetyl cellulose, nitrocellulose, starch, calcium alginate,
hydroxypropyl methyl cellulose and the like; chitin; chitosan;
urushi (Japanese lacquer); polyamides such as gelatin, collagen,
keratin and the like; and copolymers of these high molecular
materials. These may be a composite compound, and metal oxide
particles, glass fiber or the like may be added thereto as occasion
demands. Further, an organic compound material may be blended
therewith.
[0174] Since the capability of attenuating radiation energy
generally increases as specific gravity increases, the support of
the stimulable phosphor sheet is preferably formed of a compound
material or a composite material having specific gravity of 1.0
g/cm.sup.3 or more and more preferably formed of a compound
material or a composite material having specific gravity of 1.5
g/cm.sup.3 to 23 g/cm.sup.3.
[0175] In a preferred aspect of the present invention, a material
capable of attenuating radiation energy has property of reducing
the energy of radiation to 1/5 or less when the radiation travels
in the material by the distance between neighboring dot-like
stimulable phosphor layer regions.
[0176] In a further preferred aspect of the present invention, the
support of the stimulable phosphor sheet is made of a material
capable of reducing the energy of radiation to {fraction (1/10)} or
less when the radiation travels in the material by the distance
between neighboring dot-like stimulable phosphor layer regions.
[0177] In a further preferred aspect of the present invention, the
support of the stimulable phosphor sheet is made of a material
capable of reducing the energy of radiation to {fraction (1/50)} or
less when the radiation travels in the material by the distance
between neighboring dot-like stimulable phosphor layer regions.
[0178] In a further preferred aspect of the present invention, the
support of the stimulable phosphor sheet is made of a material
capable of reducing the energy of radiation to {fraction (1/100)}
or less when the radiation travels in the material by the distance
between neighboring dot-like stimulable phosphor layer regions.
[0179] In a further preferred aspect of the present invention, the
support of the stimulable phosphor sheet is made of a material
capable of reducing the energy of radiation to {fraction (1/500)}
or less when the radiation travels in the material by the distance
between neighboring dot-like stimulable phosphor layer regions.
[0180] In a further preferred aspect of the present invention, the
support of the stimulable phosphor sheet is made of a material
capable of reducing the energy of radiation to {fraction (1/1000)}
or less when the radiation travels in the material by the distance
between neighboring dot-like stimulable phosphor layer regions.
[0181] The above and other objects of the present invention can
also be accomplished by a biochemical analyzing method comprising
the steps of preparing a stimulable phosphor sheet including a
support, selectively storing radiation energy in a plurality of
stimulable phosphor layer regions formed at least one-dimensionally
and spaced-apart from each other in the support, moving the
stimulable phosphor sheet and a stimulating ray relative to each
other in at least a main scanning direction, sequentially
irradiating the plurality of stimulable phosphor layer regions with
the stimulating ray, thereby exciting stimulable phosphor contained
in the plurality of stimulable phosphor layer regions,
photoelectrically detecting stimulated emission released from the
stimulable phosphor, thereby producing analog data, converting the
analog data to digital data and producing biochemical analysis
data.
[0182] According to this aspect of the present invention, since
biochemical analysis data are produced by selectively storing
radiation energy in a plurality of stimulable phosphor layer
regions formed at least one-dimensionally and spaced-apart from
each other in the support, moving the stimulable phosphor sheet and
a stimulating ray relative to each other in at least a main
scanning direction, sequentially irradiating the plurality of
stimulable phosphor layer regions with the stimulating ray, thereby
exciting stimulable phosphor contained in the plurality of
stimulable phosphor layer regions, photoelectrically detecting
stimulated emission released from the stimulable phosphor, thereby
producing analog data, and converting the analog data to digital
data, it is possible to produce biochemical analysis data with high
resolving power and high quantitative accuracy.
[0183] In a preferred aspect of the present invention, the
plurality of stimulable phosphor layer regions are formed
two-dimensionally and spaced-apart from each other in the support
and biochemical analysis data are produced by moving the stimulable
phosphor sheet and the stimulating ray relative to each other in
the main scanning direction and a sub-scanning direction
perpendicular to the main scanning direction, sequentially
irradiating the plurality of stimulable phosphor layer regions with
the stimulating ray, thereby exciting stimulable phosphor contained
in the plurality of stimulable phosphor layer regions,
photoelectrically detecting stimulated emission released from the
stimulable phosphor, thereby producing analog data, and converting
the analog data to digital data.
[0184] According to this preferred aspect of the present invention,
since the stimulable phosphor layer regions can be formed at a high
density, biochemical analysis data can be efficiently produced.
[0185] In a preferred aspect of the present invention, a laser beam
is used as a stimulating ray and stimulable phosphor contained in
the plurality of stimulable phosphor layer regions is excited by
moving the stimulable phosphor sheet and the laser beam relative to
each other in the main scanning direction and a sub-scanning
direction perpendicular to the main scanning direction, and
sequentially irradiating the plurality of stimulable phosphor layer
regions with the laser beam.
[0186] In a preferred aspect of the present invention, the
stimulable phosphor sheet is moved in the main scanning
direction.
[0187] In another preferred aspect of the present invention, the
stimulating ray is moved in the main scanning direction.
[0188] In the present invention, the stimulable phosphor usable in
the present invention may be of any type insofar as it can store
radiation energy or electron beam energy and can be stimulated by
an electromagnetic wave to release the radiation energy or the
electron beam energy stored therein in the form of light. More
specifically, preferably employed stimulable phosphors include
alkaline earth metal fluorohalide phosphors (Ba.sub.1-x,
M.sup.2+.sub.x)FX:yA (where M.sup.2+ is at least one alkaline earth
metal selected from the group consisting of Mg, Ca, Sr, Zn and Cd;
X is at least one element selected from the group consisting of Cl,
Br and I, A is at least one element selected from the group
consisting of Eu, Tb, Ce, Tm, Dy, Pr, Ho, Nd, Yb and Er; x is equal
to or greater than 0 and equal to or less than 0.6 and y is equal
to or greater than 0 and equal to or less than 0.2) disclosed in
U.S. Pat. No. 4,239,968, alkaline earth metal fluorohalide
phosphors SrFX:Z (where X is at least one halogen selected from the
group consisting of Cl, Br and I; Z is at least one Eu and Ce)
disclosed in Japanese Patent Application Laid Open No. 2-276997,
europium activated complex halide phosphors BaFXxNaX':aEu.sup.2+
(where each of X or X' is at least one halogen selected from the
group consisting of Cl, Br and I; x is greater than 0 and equal to
or less than 2; and y is greater than 0 and equal to or less than
0.2) disclosed in Japanese Patent Application Laid Open No.
59-56479, cerium activated trivalent metal oxyhalide phosphors
MOX:xCe (where M is at least one trivalent metal selected from the
group consisting of Pr, Nd, Pm, Sm, Eu, Tb, Dy, Ho, Er, Tm, Yb and
Bi; X is at least one halogen selected from the group consisting of
Br and I; and x is greater than 0 and less than 0.1) disclosed in
Japanese Patent Application laid Open No. 58-69281, cerium
activated rare earth oxyhalide phosphors LnOX:xCe (where Ln is at
least one rare earth element selected from the group consisting of
Y, La, Gd and Lu; X is at least one halogen selected from the group
consisting of Cl, Br and I; and x is greater than 0 and equal to or
less than 0.1) disclosed in U.S. Pat. No. 4,539,137, and europium
activated complex halide phosphors M.sup.IIFXaM.sup.IX'bM'.s-
up.IIX".sub.2cM.sup.IIIX'".sub.3xA:yEu.sup.2+ (where M.sup.II is at
least one alkaline earth metal selected from the group consisting
of Ba, Sr and Ca; M.sup.I is at least one alkaline metal selected
from the group consisting of Li, Na, K, Rb and Cs; M'.sup.II is at
least one divalent metal selected from the group consisting of Be
and Mg; M.sup.III is at least one trivalent metal selected from the
group consisting of Al, Ga, In and Ti; Ais at least one metal
oxide; X is at least one halogen selected from the group consisting
of Cl, Br and I; each of X', X" and X'" is at least one halogen
selected from the group consisting of F, Cl, Br and I; a is equal
to or greater than 0 and equal to or less than 2; b is equal to or
greater than 0 and equal to or less than 10.sup.-2; c is equal to
or greater than 0 and equal to or less than 10.sup.-2; a+b+c is
equal to or greater than 10.sup.-2; x is greater than 0 and equal
to or less than 0.5; and y is greater than 0 and equal to or less
than 0.2) disclosed in U.S. Pat. No. 4,962,047.
[0189] In a preferred aspect of the present invention, specific
binding substances may be spotted onto the absorptive regions of a
biochemical analysis unit using a spotting device.
[0190] In a preferred aspect of the present invention, a spotting
device includes a base plate onto which a biochemical analysis
unit, on which specific binding substances are to be spotted, is to
be placed, a spotting head capable of spotting specific binding
substances, and sensor means for detecting a reference position of
the absorptive region to which specific binding substances are to
be spotted.
[0191] In a preferred aspect of the present invention, a spotting
device further includes a drive mechanism for at least
one-dimensionally and intermittently moving the spotting head and
the base plate relative to each other.
[0192] According to this preferred aspect of the present invention,
since a spotting device further includes a drive mechanism for at
least one-dimensionally and intermittently moving the spotting head
and the base plate relative to each other, specific binding
substances can be reliably spotted onto the absorptive regions
formed in a biochemical analysis unit in at least one-dimension by
using the sensor means to detect the absorptive regions of the
biochemical analysis unit placed on the base plate for spotting
with specific binding substances, thereby determining the relative
positional relationship between the spotting head of the spotting
device and the base plate on which the biochemical analysis unit is
placed, and spotting specific binding substances from the spotting
head, while operating the driving mechanism for at least one
dimensionally and intermittently moving the spotting head and the
base plate relative to each other.
[0193] In a further preferred aspect of the present invention, the
drive mechanism is adapted for at least one-dimensionally moving
the spotting head and the base plate relative to each other at a
constant pitch.
[0194] According to this preferred aspect of the present invention,
since the drive mechanism is adapted for at least one-dimensionally
moving the spotting head and the base plate relative to each other
at a constant pitch, specific binding substances can be reliably
spotted onto the absorptive regions formed in a biochemical
analysis unit in at least one-dimension by using the sensor means
to detect the absorptive regions of the biochemical analysis unit
placed on the base plate for spotting with specific binding
substances, thereby determining the relative positional
relationship between the spotting head of the spotting device and
the base plate on which the biochemical analysis unit is placed,
and spotting specific binding substances from the spotting head,
while operating the driving mechanism for at least one
dimensionally moving the spotting head and the base plate relative
to each other at a constant pitch.
[0195] In a further preferred aspect of the present invention, the
drive mechanism is adapted for relatively and intermittently moving
the spotting head and the base in two dimensions.
[0196] According to this preferred aspect of the present invention,
since the drive mechanism is adapted for relatively and
intermittently moving the spotting head and the base in two
dimensions, specific binding substances can be reliably spotted
onto the absorptive regions two-dimensionally formed in a
biochemical analysis unit by using the sensor means to detect the
absorptive regions of the biochemical analysis unit placed on the
base plate for spotting with specific binding substances, thereby
determining the relative positional relationship between the
spotting head of the spotting device and the base plate on which
the biochemical analysis unit is placed, and spotting specific
binding substances from the spotting head, while operating the
driving mechanism for relatively and intermittently moving the
spotting head and the base plate in two dimensions.
[0197] In a further preferred aspect of the present invention, the
drive mechanism is adapted for relatively and intermittently moving
the spotting head and the base at a constant pitch in two
dimensions.
[0198] According to this preferred aspect of the present invention,
since the drive mechanism is adapted for relatively and
intermittently moving the spotting head and the base at a constant
pitch in two dimensions, specific binding substances can be
reliably spotted onto the absorptive regions two-dimensionally
formed in a biochemical analysis unit by using the sensor means to
detect the absorptive regions of the biochemical analysis unit
placed on the base plate for spotting with specific binding
substances, thereby determining the relative positional
relationship between the spotting head of the spotting device and
the base plate on which the biochemical analysis unit is placed,
and spotting specific binding substances from the spotting head,
while operating the driving mechanism for relatively and
intermittently moving the spotting head and the base plate at a
constant pitch in two dimensions.
[0199] In a preferred aspect of the present invention, at least two
positioning members are formed in the base plate for positioning a
biochemical analysis unit.
[0200] According to this preferred aspect of the present invention,
since at least two positioning members are formed in the base plate
for positioning a biochemical analysis unit, it is possible to
position the biochemical analysis unit onto which specific binding
substances are to be spotted at a predetermined position of the
base plate and set it on the base plate.
[0201] In a further preferred aspect of the present invention, each
of the positioning members is constituted as a pin uprightly formed
on the base plate.
[0202] According to this preferred aspect of the present invention,
since each of the positioning members is constituted as a pin
uprightly formed on the base plate, it is possible to easily
position the biochemical analysis unit onto which specific binding
substances are to be spotted at a predetermined position of the
base plate and set it on the base plate by forming the biochemical
analysis unit with positioning through-holes corresponding to the
pins.
[0203] In a preferred aspect of the present invention, the spotting
device further includes positional data calculating means for
calculating positional data of the absorptive regions of the
biochemical analysis unit onto which specific binding substances
are to be spotted based on at least two reference positions of the
biochemical analysis unit detected by the sensor means, a memory
for storing the positional data of the absorptive regions of the
biochemical analysis unit onto which specific binding substances
are to be spotted calculated by the positional data calculating
means, and position control means for controlling the drive
mechanism in accordance with the positional data of the absorptive
regions of the biochemical analysis unit onto which specific
binding substances are to be spotted stored in the memory.
[0204] According to this preferred aspect of the present invention,
since the spotting device further includes positional data
calculating means for calculating positional data of the absorptive
regions of the biochemical analysis unit onto which specific
binding substances are to be spotted based on at least two
references positions of the biochemical analysis unit detected by
the sensor means, a memory for storing the positional data of the
absorptive regions of the biochemical analysis unit onto which
specific binding substances are to be spotted calculated by the
positional data calculating means, and position control means for
controlling the drive mechanism in accordance with the positional
data of the absorptive regions of the biochemical analysis unit
onto which specific binding substances are to be spotted stored in
the memory, it is possible to automatically spot specific binding
substances onto a plurality of absorptive regions spaced-apart and
dot-like formed in the substrate.
[0205] The above and other objects and features of the present
invention will become apparent from the following description made
with reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0206] FIG. 1 is a schematic perspective view showing a biochemical
analysis unit which is a preferred embodiment of the present
invention.
[0207] FIG. 2 is a schematic front view showing a spotting
device.
[0208] FIG. 3 is a schematic front view showing a hybridization
vessel.
[0209] FIG. 4 is a schematic perspective view showing a stimulable
phosphor sheet.
[0210] FIG. 5 is a schematic cross-sectional view showing a method
for exposing a number of dot-like stimulable phosphor layer regions
formed on a stimulable phosphor sheet by a radioactive labeling
substance contained in absorptive regions formed in a number of
through-holes.
[0211] FIG. 6 is a schematic perspective view showing one example
of a scanner for reading radiation data of a radioactive labeling
substance recorded in a number of stimulable phosphor layer regions
formed on a stimulable phosphor sheet and fluorescence data
recorded in absorptive regions formed in a number of holes of a
biochemical analysis unit and producing biochemical analysis
data.
[0212] FIG. 7 is a schematic perspective view showing details in
the vicinity of a photomultiplier.
[0213] FIG. 8 is a schematic cross-sectional view taken along a
line A-A in FIG. 7.
[0214] FIG. 9 is a schematic cross-sectional view taken along a
line B-B in FIG. 7.
[0215] FIG. 10 is a schematic cross-sectional view taken along a
line C-C in FIG. 7.
[0216] FIG. 11 is a schematic cross-sectional view taken along a
line D-D in FIG. 7.
[0217] FIG. 12 is a schematic plan view of a scanning mechanism of
an optical head.
[0218] FIG. 13 is a block diagram of a control system, an input
system and a drive system of a scanner shown in FIG. 6.
[0219] FIG. 14 is a schematic front view showing a data producing
system for reading chemiluminescent data of a labeling substance,
recorded in absorptive regions formed in a number of through-holes
of a biochemical analysis unit, which generates chemiluminescent
emission when it contacts a chemiluminescent substrate and
producing a biochemical analysis data.
[0220] FIG. 15 is a schematic longitudinal cross sectional view
showing a cooled CCD camera.
[0221] FIG. 16 is a schematic vertical cross sectional view showing
a dark box.
[0222] FIG. 17 is a block diagram of a personal computer and
peripheral devices thereof.
[0223] FIG. 18 is a schematic vertical cross sectional view showing
another example of a dark box.
[0224] FIG. 19 is a schematic longitudinal cross sectional view
showing a biochemical analysis unit which is another embodiment of
the present invention.
[0225] FIG. 20 is a schematic cross-sectional view showing a method
for exposing a number of dot-like stimulable phosphor layer regions
formed on a stimulable phosphor sheet by a radioactive labeling
substance contained in absorptive regions formed on a porous
substrate.
[0226] FIG. 21 is a schematic perspective view of a biochemical
analysis unit which is a further preferred embodiment of the
present invention.
[0227] FIG. 22 is a schematic plan view showing another example of
a spotting device.
[0228] FIG. 23 is a block diagram showing a control system, an
input system, a drive system and a detection system of a spotting
device.
[0229] FIG. 24 is a schematic partial plan view showing a
biochemical analysis unit in which specific binding substances are
spotted from an injector located a reference position thereof.
[0230] FIG. 25 is a schematic perspective view of a biochemical
analysis unit which is a further preferred embodiment of the
present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0231] FIG. 1 is a schematic perspective view showing a biochemical
analysis unit which is a preferred embodiment of the present
invention.
[0232] As shown in FIG. 1, a biochemical analysis unit 1 includes a
substrate 2 formed of metal such as aluminum capable of attenuating
radiation energy and light energy and having flexibility and formed
with a number of substantially circular through-holes 3, and
absorptive material 4 such as nylon-6 is charged in the
through-holes 3.
[0233] Although not accurately shown in FIG. 1, in this embodiment,
about 10,000 through-holes 3 having a size of about 0.01 cm.sup.2
are regularly formed at a density of about 10,000 per cm.sup.2 in
the substrate 2.
[0234] FIG. 2 is a schematic front view showing a spotting
device.
[0235] When biochemical analysis is performed, as shown in FIG. 2,
specific binding substances such as a plurality of cDNAs whose
sequences are known but are different from each other are spotted
using a spotting device onto the porous material 4 charged in a
number of the through-holes 3 of the biochemical analysis unit
1.
[0236] As shown in FIG. 2, the spotting head 5 of the spotting
device includes an injector 6 for ejecting a solution of specific
binding substances toward the biochemical analysis unit 1 and a CCD
camera 7 and is constituted so that cDNAs are spotted from the
injector 6 when the tip end portion of the injector 6 and the
center of the through-hole 3 into which a specific binding
substance is to be spotted are determined to coincide with each
other as a result of viewing them using the CCD camera, thereby
ensuring that cDNAs can be accurately spotted into the through-hole
3 in which porous material is charged.
[0237] FIG. 3 is a schematic front view showing a hybridization
vessel.
[0238] As shown in FIG. 3, a hybridization vessel 8 is formed
cylindrically and accommodates a hybridization solution 9
containing a substance derived from a living organism labeled with
a labeling substance therein.
[0239] In the case where a specific binding substance such as cDNA
is to be labeled with a radioactive labeling substance, a
hybridization solution 9 containing a substance derived from a
living organism labeled with a radioactive labeling substance is
prepared and is accommodated in the hybridization vessel 8.
[0240] On the other hand, in the case where a specific binding
substance such as cDNA is to be labeled with a labeling substance
which generates chemiluminescent emission when it contacts a
chemiluminescent substrate, a hybridization solution 9 containing a
substance derived from a living organism labeled with a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate is prepared and is
accommodated in the hybridization vessel 8.
[0241] Further, in the case where a specific binding substance such
as cDNA is to be labeled with a fluorescent substance such as a
fluorescent dye, a hybridization solution 9 containing a substance
derived from a living organism labeled with a fluorescent substance
such as a fluorescent dye is prepared and is accommodated in the
hybridization vessel 8.
[0242] It is possible to prepare a hybridization solution 9
containing two or more substances derived from a living organism
among a substance derived from a living organism labeled with a
radioactive labeling substance, a substance derived from a living
organism labeled with a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate and a substance derived from a living organism labeled
with a fluorescent substance such as a fluorescent dye and
accommodate it in the hybridization vessel 8. In this embodiment, a
hybridization solution 9 containing a substance derived from a
living organism labeled with a radioactive labeling substance, a
substance derived from a living organism labeled with a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate and a substance derived from
a living organism labeled with a fluorescent substance such as a
fluorescent dye is prepared and accommodated in the hybridization
vessel 8.
[0243] When hybridization is to be performed, the biochemical
analysis unit 1 containing specific binding substances such as a
plurality of cDNAs spotted into a number of through-holes 3 in
which porous material is charged is accommodated in the
hybridization vessel 8. In this embodiment, since the substrate 2
is formed of a metal having flexibility, as shown in FIG. 3, the
biochemical analysis unit 1 can be bent and accommodated in the
hybridization vessel 8 along the inner wall surface thereof.
[0244] As shown in FIG. 3, the hybridization vessel 8 is
constituted so as to be rotatable about a shaft by a drive means
(not shown) and since the biochemical analysis unit 1 is bent and
accommodated in the hybridization vessel 8 along the inner wall
surface thereof, even when the hybridization vessel 8 accommodates
only a small amount of hybridization solution 9, specific binding
substances spotted in a number of the through-holes 3 charged with
porous material can be selectively hybridized with a substance
derived from a living organism labeled with a radioactive labeling
substance, a substance derived from a living organism labeled with
a labeling substance which generates chemiluminescent emission when
it contacts a chemiluminescent substrate and a substance derived
from a living organism labeled with a fluorescent substance such as
a fluorescent dye by rotating the hybridization vessel 8.
[0245] As a result of the hybridization, fluorescence data of a
fluorescent substance such as a fluorescent dye and
chemiluminescence data of a substance derived from a living
organism labeled with a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate are recorded in the porous material 4 charged in a number
of the through-holes 3 of the biochemical analysis unit 1.
Fluorescence data recorded in the porous material 4 are read by a
scanner described later, thereby producing biochemical analysis
data and chemiluminescence data recorded in the porous material 4
are read by a data producing system described later, thereby
producing biochemical analysis data.
[0246] FIG. 4 is a schematic perspective view showing a stimulable
phosphor sheet.
[0247] As shown in FIG. 4, a stimulable phosphor sheet 10 includes
a support 11 and one surface of the support 11 is formed with a
number of dot-like substantially circular stimulable phosphor layer
regions 12 in the same regular pattern as that of a number of
through-holes 3 formed in the biochemical analysis unit 1.
[0248] In this embodiment, the support 11 is formed of stainless
capable of attenuating radiation energy.
[0249] FIG. 5 is a schematic cross-sectional view showing a method
for exposing a number of dot-like stimulable phosphor layer regions
12 formed on the stimulable phosphor sheet 10 to a radioactive
labeling substance contained in the absorptive regions 4 formed in
a number of through-holes 3.
[0250] As shown in FIG. 5, when the stimulable phosphor sheet 10 is
to be exposed, the stimulable phosphor sheet 10 is superposed on
the biochemical analysis unit 1 in such a manner that each of the
dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 is located in one of the many
through-holes 3 formed in the biochemical analysis unit 1 and that
the surface of each of the dot-like stimulable phosphor layer
regions 12 comes into close contact with the surface of the porous
material 4 charged in one of the through-holes 3.
[0251] In this embodiment, since the substrate 2 of the biochemical
analysis unit 1 is formed of a metal, it is hardly stretched and
shrunk even when it is subjected to liquid processing such as
hybridization and, therefore, it is possible to easily and
accurately superpose the stimulable phosphor sheet 10 on the
biochemical analysis unit 1 so that each of the dot-like stimulable
phosphor layer regions 12 formed in the stimulable phosphor sheet
10 is located in one of the many through-holes 3 formed in the
biochemical analysis unit 1 and that the surface of each of the
dot-like stimulable phosphor layer regions 12 comes into close
contact with the surface of the porous material 4 charged in one of
the through-holes 3, thereby exposing the dot-like stimulable
phosphor layer regions 12.
[0252] In this manner, the surface of each of the dot-like
stimulable phosphor layer regions 12 is kept in close contact with
the surface of the porous material 4 charged in one of the
through-holes 3 for a predetermined time period, whereby a number
of the dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 are exposed to the radioactive
labeling substance contained in the porous material 4.
[0253] During the exposure operation, electron beams are released
from the radioactive labeling substance. However, since the
substrate 2 is formed of a metal capable of attenuating radiation
energy and light energy, electron beams released from the
radioactive labeling substance are prevented from being scattered
in the substrate 2. Further, since each of a number of dot-like
stimulable phosphor layer regions 12 formed in the stimulable
phosphor sheet 10 is located in one of the many through-holes 3
formed in the biochemical analysis unit 1, the electron beams
released from the radioactive labeling substance is prevented from
being scattered in the dot-like stimulable phosphor layer region 12
and advancing to the dot-like stimulable phosphor layer region 12
located in neighboring through-holes.
[0254] Moreover, since the support 11 of the stimulable phosphor
sheet 10 is formed of stainless capable of attenuating radiation
energy in this embodiment, the electron beams can be also prevented
from being scattered in the support 11 of the stimulable phosphor
sheet 10 to enter neighboring dot-like stimulable phosphor layers
region 12.
[0255] Therefore, it is possible to reliably expose a number of the
dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 to only the radioactive labeling
substance contained in the porous material 4 charged in the
corresponding through-holes 3.
[0256] In this manner, radiation data of a radioactive labeling
substance are recorded in a number of the dot-like stimulable
phosphor layer regions 12 formed in the stimulable phosphor sheet
10.
[0257] FIG. 6 is a schematic perspective view showing one example
of a scanner for reading radiation data of a radioactive labeling
substance recorded in a number of the dot-like stimulable phosphor
layer regions 12 formed on the stimulable phosphor sheet 10 and
fluorescence data recorded in the absorptive regions 4 formed in a
number of through-holes 3 of the biochemical analysis unit 1 and
producing biochemical analysis data, and FIG. 7 is a schematic
perspective view showing details in the vicinity of a
photomultiplier.
[0258] The scanner shown in FIG. 6 is constituted so as to read
radiation data of a radioactive labeling substance recorded in a
number of the dot-like stimulable phosphor layer regions 12 formed
on the stimulable phosphor sheet 10 and fluorescence data recorded
in the porous material 4 charged in a number of through-holes 3
formed in the biochemical analysis unit 1 and includes a first
laser stimulating ray source 21 for emitting a laser beam having a
wavelength of 640 nm, a second laser stimulating ray source 22 for
emitting a laser beam having a wavelength of 532nm and a third
laser stimulating ray source 23 for emitting a laser beam having a
wavelength of 473 nm. In this embodiment, the first laser
stimulating ray source 21 constituted by a semiconductor laser beam
source and the second laser stimulating ray source 22 and the third
laser stimulating ray source 23 are constituted by a second
harmonic generation element.
[0259] A laser beam 24 emitted from the first laser stimulating
source 21 passes through a collimator lens 25, thereby being made a
parallel beam, and is reflected by a mirror 26. A first dichroic
mirror 27 for transmitting light having a wavelength of 640 nm but
reflecting light having a wavelength of 532 nm and a second
dichroic mirror 28 for transmitting light having a wavelength equal
to and longer than 532 nm but reflecting light having a wavelength
of 473 nm are provided in the optical path of the laser beam 24
emitted from the first laser stimulating ray source 21. The laser
beam 24 emitted from the first laser stimulating ray source 21 and
reflected by the mirror 26 passes through the first dichroic mirror
27 and the second dichroic mirror 28 and advances to a mirror
29.
[0260] On the other hand, the laser beam 24 emitted from the second
laser stimulating ray source 22 passes through a collimator lens
30, thereby being made a parallel beam, and is reflected by the
first dichroic mirror 27, thereby changing its direction by 90
degrees. The laser beam 24 then passes through the second dichroic
mirror 28 and advances to the mirror 29.
[0261] Further, the laser beam 24 emitted from the third laser
stimulating ray source 23 passes through a collimator lens 31,
thereby being made a parallel beam, and is reflected by the second
dichroic mirror 28, thereby changing its direction by 90 degrees.
The laser beam 24 then advances to the mirror 29.
[0262] The laser beam 24 advancing to the mirror 29 is reflected by
the mirror 29 and advances to a mirror 32 to be reflected
thereby.
[0263] A perforated mirror 34 formed with a hole 33 at the center
portion thereof is provided in the optical path of the laser beam
24 reflected by the mirror 32. The laser beam 4 reflected by the
mirror 32 passes through the hole 33 of the perforated mirror 34
and advances to a concave mirror 38.
[0264] The laser beam 24 advancing to the concave mirror 38 is
reflected by the concave mirror 38 and enters an optical head
35.
[0265] The optical head 35 includes a mirror 36 and an aspherical
lens 37. The laser beam 24 entering the optical head 35 is
reflected by the mirror 36 and condensed by the aspherical lens 37
onto the stimulable phosphor sheet 10 or the biochemical analysis
unit 1 placed on the glass plate 41 of the stage 40. In FIG. 6, the
biochemical analysis unit 1 is placed on the glass plate 41 of the
stage 40 in such a manner that the side of the porous material 4
into which a specific binding substance is dropped is directed
downward.
[0266] When the laser beam 24 impinges on the dot-like stimulable
phosphor layer region 12 of the stimulable phosphor 10, stimulable
phosphor contained in the dot-like stimulable phosphor layer region
12 formed on the stimulable phosphor 10 is excited, thereby
releasing stimulated emission 45. On the other hand, when the laser
beam 24 impinges on the biochemical analysis unit 1, a fluorescent
dye or the like contained in the porous material 4 in a number of
the through-holes 3 is excited, thereby releasing fluorescence
45.
[0267] The stimulated emission 45 released from the dot-like
stimulable phosphor layer region 12 of the stimulable phosphor 10
or the fluorescence 45 released from the porous material 4 in a
number of the through-holes 3 of the biochemical analysis unit 1 is
condensed onto the mirror 36 by the aspherical lens 37 provided in
the optical head 35 and reflected by the mirror 36 on the side of
the optical path of the laser beam 24, thereby being made a
parallel beam to advance to the concave mirror 38.
[0268] The stimulated emission 45 or the fluorescence 45 advancing
to the concave mirror 38 is reflected by the concave mirror 38 and
advances to the perforated mirror 34.
[0269] As shown in FIG. 7, the stimulated emission 45 or the
fluorescence 45 advancing to the perforated mirror 34 is reflected
downward by the perforated mirror 34 formed as a concave mirror and
advances to a filter unit 48, whereby light having a predetermined
wavelength is cut. The stimulated emission 45 or the fluorescence
45 then impinges on a photomultiplier 50, thereby being
photoelectrically detected.
[0270] As shown in FIG. 7, the filter unit 48 is provided with four
filter members 51a, 51b, 51c and 51d and is constituted to be
laterally movable in FIG. 7 by a motor (not shown).
[0271] FIG. 8 is a schematic cross-sectional view taken along a
line A-A in FIG. 7.
[0272] As shown in FIG. 8, the filter member 51a includes a filter
52a and the filter 52a is used for reading fluorescence 45 by
stimulating a fluorescent substance such as a fluorescent dye
contained in the porous material 4 in a number of through-holes 3
of the biochemical analysis unit 1 using the first laser
stimulating ray source 21 and has a property of cutting off light
having a wavelength of 640 nm but transmitting light having a
wavelength longer than 640 nm.
[0273] FIG. 9 is a schematic cross-sectional view taken along a
line B-B in FIG. 7.
[0274] As shown in FIG. 9, the filter member 51b includes a filter
52b and the filter 52b is used for reading fluorescence 45 by
stimulating a fluorescent substance such as a fluorescent dye
contained in the porous material 4 in a number of through-holes 3
of the biochemical analysis unit 1 using the second laser
stimulating ray source 22 and has a property of cutting off light
having a wavelength of 532 nm but transmitting light having a
wavelength longer than 532 nm.
[0275] FIG. 10 is a schematic cross-sectional view taken along a
line C-C in FIG. 7.
[0276] As shown in FIG. 10, the filter member 51a includes a filter
52c and the filter 52c is used for reading fluorescence 45 by
stimulating a fluorescent substance such as a fluorescent dye
contained in the porous material 4 in a number of through-holes 3
of the biochemical analysis unit 1 using the third laser
stimulating ray source 23 and has a property of cutting off light
having a wavelength of 473 nm but transmitting light having a
wavelength longer than 473 nm.
[0277] FIG. 11 is a schematic cross-sectional view taken along a
line D-D in FIG. 7.
[0278] As shown in FIG. 11, the filter member 51d includes a filter
52d and the filter 52d is used for reading stimulated emission
released from stimulable phosphor contained in the dot-like
stimulable phosphor layer regions 12 formed on the stimulable
phosphor sheet 10 upon being stimulated using the first laser
stimulating ray source 1 and has a property of transmitting only
light having a wavelength corresponding to that of stimulated
emission emitted from stimulable phosphor but cutting off light
having a wavelength of 640 nm.
[0279] Therefore, in accordance with the kind of a stimulating ray
source to be used, one of these filter members 51a, 51b, 51c, 51d
is selectively positioned in front of the photomultiplier 50,
thereby enabling the photomultiplier 50 to photoelectrically detect
only light to be detected.
[0280] The analog data produced by photoelectrically detecting
light with the photomultiplier 50 are converted by an A/D converter
53 into digital data and the digital data are fed to a data
processing apparatus 54.
[0281] Although not shown in FIG. 6, the optical head 35 is
constituted to be movable by a scanning mechanism in the X
direction and the Y direction in FIG. 6 so that all of the dot-like
stimulable phosphor layer regions 12 formed on the stimulable
phosphor sheet 10 or the whole surface of the biochemical analysis
unit 1 can be scanned by the laser beam 24.
[0282] FIG. 12 is a schematic plan view showing the scanning
mechanism of the optical head 35. In FIG. 12, optical systems other
than the optical head 35 and the paths of the laser beam 24 and
stimulated emission 45 or fluorescence 45 are omitted for
simplification.
[0283] As shown in FIG. 12, the scanning mechanism of the optical
head 35 includes a base plate 60, and a sub-scanning pulse motor 61
and a pair of rails 62, 62 are fixed on the base plate 60. A
movable base plate 63 is further provided so as to be movable in
the sub-scanning direction indicated by an arrow Y in FIG. 12.
[0284] The movable base plate 63 is formed with a threaded hole
(not shown) and a threaded rod 64 rotated by the sub-scanning pulse
motor 61 is engaged with the inside of the hole.
[0285] A main scanning pulse motor 65 is provided on the movable
base plate 63. The main scanning pulse motor 65 is adapted for
driving an endless belt 66. The optical head 35 is fixed to the
endless belt 66 and when the endless belt 66 is driven by the main
scanning pulse motor 65, the optical head 35 is moved in the main
scanning direction indicated by an arrow X in FIG. 12. In FIG. 12,
the reference numeral 67 designates a linear encoder for detecting
the position of the optical head 35 in the main scanning direction
and the reference numeral 68 designates slits of the linear encoder
67.
[0286] Therefore, the optical head 35 is moved in the X direction
and the Y direction in FIG. 12 by driving the endless belt 66 in
the main scanning direction by the main scanning pulse motor 65 and
moving the movable base plate 63 in the sub-scanning direction by
the sub-scanning pulse motor 61, thereby scanning all of the
dot-like stimulable phosphor layer regions 12 formed on the
stimulable phosphor sheet 10 or the whole surface of the
biochemical analysis unit 1 with the laser beam 24.
[0287] FIG. 13 is a block diagram of a control system, an input
system and a drive system of the scanner shown in FIG. 6.
[0288] As shown in FIG. 13, the control system of the scanner
includes a control unit 70 for controlling the whole operation of
the scanner and the input system of the scanner includes a keyboard
71 which can be operated by an operator and through which various
instruction signals can be input.
[0289] As shown in FIG. 13, the drive system of the scanner
includes a filter unit motor 72 for moving the filter unit 48
provided with the four filter members 51a, 51b, 51c and 51d.
[0290] The control unit 70 is adapted for selectively outputting a
drive signal to the first laser stimulating ray source 21, the
second laser stimulating ray source 22 or the third laser
stimulating ray source 23 and outputting a drive signal to the
filter unit motor 72.
[0291] The thus constituted scanner reads fluorescence data of a
fluorescent substance such as a fluorescent dye carried in the
porous material 4 charged in a number of through-holes 3 formed in
the biochemical analysis unit 1 and produces biochemical analysis
data in the following manner.
[0292] A biochemical analysis unit 1 is first set on the glass
plate 41 of the stage 40 by an operator.
[0293] The kind of fluorescent substance as a labeling substance is
then input through the keyboard 71 by the operator and an
instruction signal indicating that fluorescence data are to be read
is input through the keyboard 71.
[0294] The instruction signal is input to the control unit 70 and
when the control unit 70 receives it, it determines the laser
stimulating ray source to be used in accordance with a table stored
in a memory (not shown) and also determines what filter is to be
positioned in the optical path of fluorescence 45 among the filters
52a, 52b and 52c.
[0295] For example, when Rhodamine (registered trademark), which
can be most efficiently stimulated by a laser beam having a
wavelength of 532 nm, is used as a fluorescent substance for
labeling a substance derived from a living organism and a signal
indicating such a fact is input, the control unit 70 selects the
second laser stimulating ray source 22 and the filter 52b and
outputs a drive signal to the filter unit motor 72, thereby moving
the filter unit 48 so that the filter member 51b inserting the
filter 52b having a property of cutting off light having a
wavelength of 532 nm but transmitting light-having a wavelength
longer than 532 nm in the optical path of the fluorescence 45.
[0296] The control unit 70 then outputs a drive signal to the
second laser stimulating ray source 22 to activate it, thereby
causing it to emit a laser beam 24 having a wavelength of 532
nm.
[0297] The laser beam 24 emitted from the second laser stimulating
ray source 22 is made a parallel beam by the collimator lens 30,
advances to the first dichroic mirror 27 and is reflected
thereby.
[0298] The laser beam 24 reflected by the first dichroic mirror 27
transmits through the second dichroic mirror 28 and enters the
mirror 29.
[0299] The laser beam 24 entering the mirror 29 is reflected by the
mirror 29 and further enters a mirror 32 to be reflected
thereby.
[0300] The laser beam 24 reflected by the mirror 32 advances to the
perforated mirror 34 and passes through the hole 33 of the
perforated mirror 34. Then, the laser beam 24 advances to the
concave mirror 38.
[0301] The laser beam 24 advancing to the concave mirror 38 is
reflected thereby and enters the optical head 35.
[0302] The laser beam 24 entering the optical head 35 is reflected
by the mirror 36 and condensed by the aspherical lens 37 onto the
biochemical analysis unit 1 placed on the glass plate 41 of the
stage 40.
[0303] As a result, a fluorescent substance such as a fluorescent
dye, for instance, Rhodamine, contained in the porous material 4
charged in a number of through-holes 3 formed in the biochemical
analysis unit 1 is stimulated by the laser beam 24 and fluorescence
45 is released from Rhodamine.
[0304] In the biochemical analysis unit 1 according to this
embodiment, since the substrate 2 of the biochemical analysis unit
1 is formed of a metal having a property capable of attenuating
radiation energy and light energy, it is possible to reliably
prevent fluorescence released from a fluorescent substance
contained in porous material 4 charged in a through-hole 3 from
being scattered in the substrate 2 and mixed with fluorescent
released from a fluorescent substance contained in porous material
4 charged in through-holes 3 neighboring the through-hole 3.
[0305] The fluorescence 45 released from Rhodamine is condensed by
the aspherical lens 37 provided in the optical head 35 and
reflected by the mirror 36 on the side of an optical path of the
laser beam 24, thereby being made a parallel beam to advance to the
concave mirror 38.
[0306] The fluorescence 45 advancing to the concave mirror 38 is
reflected by the concave mirror 38 and advances to the perforated
mirror 34.
[0307] As shown in FIG. 7, the fluorescence 45 advancing to the
perforated mirror 34 is reflected downward by the perforated mirror
34 formed as a concave mirror and advances to the filter 52b of a
filter unit 48.
[0308] Since the filter 52b has a property of cutting off light
having a wavelength of 532 nm but transmitting light having a
wavelength longer than 532 nm, light having the same wavelength of
532 nm as that of the stimulating ray is cut off by the filter 52b
and only light in the wavelength of the fluorescence 45 released
from Rhodamine passes through the filter 52b to be
photoelectrically detected by the photomultiplier 50.
[0309] As described above, since the optical head 35 is moved on
the base plate 63 in the X direction in FIG. 12 by the main
scanning pulse motor 65 mounted on the base plate 63 and the base
plate 63 is moved in the Y direction in FIG. 12 by the sub-scanning
pulse motor 61, the whole surface of the biochemical analysis unit
1 is scanned by the laser beam 24. Therefore, the photomultiplier
50 can read fluorescent data of Rhodamine recorded in the
biochemical analysis unit 1 by photoelectrically detecting the
fluorescence 45 released from Rhodamine contained in the porous
material in a number of through-holes 3 and produce analog data for
biochemical analysis.
[0310] The analog data produced by photoelectrically detecting the
stimulated emission 45 with the photomultiplier 50 are converted by
the AID converter 53 into digital data and the digital data are fed
to the data processing apparatus 54.
[0311] On the other hand, when radiation data recorded in a
stimulable phosphor sheet 10 by exposing the dot-like stimulable
phosphor layer regions 12 to a radioactive labeling substance
contained in the porous material in a number of through-holes 3
formed in the biochemical analysis unit 1 are to be read to produce
biochemical analysis data, the stimulable phosphor sheet 10 is
placed on the glass plate 41 of the stage 40 in such a manner that
the dot-like stimulable phosphor layer regions 12 come into contact
with the glass plate 41.
[0312] An instruction signal indicating that radiation data
recorded in the dot-like stimulable phosphor layer regions 12
formed on the stimulable phosphor sheet 10 are to be read is then
input through the keyboard 71.
[0313] The instruction signal input through the keyboard 71 is
input to the control unit 70 and the control unit 70 outputs a
drive signal to the filter unit motor 72 in accordance with the
instruction signal, thereby moving the filter unit 48 so as to
locate the filter member 51d provided with the filter 52d having a
property of transmitting only light having a wavelength
corresponding to that of stimulated emission emitted from
stimulable phosphor but cutting off light having a wavelength of
640 nm in the optical path of stimulated emission 45.
[0314] The control unit 70 then outputs a drive signal to the first
laser stimulating ray source 21 to activate it, thereby causing it
to emit a laser beam 24 having a wavelength of 640 nm.
[0315] The laser beam 24 emitted from the first laser stimulating
ray source 21 is made a parallel beam by the collimator lens 25
and-advances to the mirror 26 to be reflected thereby.
[0316] The laser beam 24 reflected by the mirror 26 passes through
the first dichroic mirror 27 and the second dichroic mirror 28 and
advances to the mirror 29.
[0317] The laser beam 24 advancing to the mirror 29 is reflected by
the mirror 29 and further advances to a mirror 32 to be reflected
thereby.
[0318] The laser beam 24 reflected by the mirror 32 passes through
the hole 33 of the perforated mirror 34 and advances to the concave
mirror 38.
[0319] The laser beam 24 advancing to the concave mirror 38 is
reflected thereby and enters the optical head 35.
[0320] The laser beam 24 entering the optical head 35 is reflected
by the mirror 36 and condensed by the aspherical lens 37 onto the
dot-like stimulable phosphor layer region 12 of the stimulable
phosphor sheet 10 placed on the glass plate 41 of the stage 40.
[0321] As a result, a stimulable phosphor contained in the dot-like
stimulable phosphor layer region 12 formed on the stimulable
phosphor sheet 10 is stimulated by the laser beam 24 and stimulated
emission 45 is released from the stimulable phosphor.
[0322] The stimulated emission 45 released from the stimulable
phosphor contained in the dot-like stimulable phosphor layer region
12 is condensed by the aspherical lens 37 provided in the optical
head 35 and reflected by the mirror 36 on the side of an optical
path of the laser beam 24, thereby being made a parallel beam to
advance to the concave mirror 38.
[0323] The stimulated emission 45 advancing to the concave mirror
38 is reflected by the concave mirror 38 and advances to the
perforated mirror 34.
[0324] As shown in FIG. 7, the stimulated emission 45 advancing to
the perforated mirror 34 is reflected downward by the perforated
mirror 34 formed as a concave mirror and advances to the filter 52d
of a filter unit 48.
[0325] Since the filter 52d has a property of transmitting only
light having a wavelength corresponding to that of stimulated
emission emitted from stimulable phosphor but cutting off light
having a wavelength of 640 nm, light having a wavelength of 640 nm
corresponding to that of the stimulating ray is cut off by the
filter 52d and only light having a wavelength corresponding to that
of stimulated emission passes through the filter 52d to be
photoelectrically detected by the photomultiplier 50.
[0326] As described above, since the optical head 35 is moved on
the base plate 63 in the X direction in FIG. 12 by the main
scanning pulse motor 65 mounted on the base plate 63 and the base
plate 63 is moved in the Y direction in FIG. 12 by the sub-scanning
pulse motor 61, all of the dot-like stimulable phosphor layer
regions 12 formed on the stimulable phosphor sheet 10 are scanned
by the laser beam 24. Therefore, the photomultiplier 50 can read
radiation data of a radioactive labeling substance recorded in a
number of the dot-like stimulable phosphor layer regions 12 by
photoelectrically detecting the stimulated emission 45 released
from stimulable phosphor contained in the stimulable phosphor layer
regions l2and produce analog data.
[0327] The analog data produced by photoelectrically detecting the
stimulated emission 45 with the photomultiplier 50 are converted by
the A/D converter 53 into digital data and the digital data are fed
to the data processing apparatus 54.
[0328] FIG. 14 is a schematic front view showing a data producing
system for reading chemiluminescent data of a labeling substance
recorded in absorptive regions formed in a number of through-holes
3 formed in the biochemical analysis unit 1, which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate and producing biochemical analysis data. The data
producing system shown in FIG. 14 is constituted to be able to also
read fluorescence data of a fluorescent substance such as a
fluorescent dye recorded in a porous material 4 charged in a number
of through-holes 3 formed in the biochemical analysis unit 1.
[0329] As shown in FIG. 14, the data producing system includes a
cooled CCD camera 81, a dark box 82 and a personal computer 83. As
shown in FIG. 14, the personal computer 83 is equipped with a CRT
84 and a keyboard 85.
[0330] FIG. 15 is a schematic longitudinal cross sectional view
showing the cooled CCD camera 81.
[0331] As shown in FIG. 15, the cooled CCD camera 81 includes a CCD
86, a heat transfer plate 87 made of metal such as aluminum, a
Peltier element 88 for cooling the CCD 86, a shutter 89 disposed in
front of the CCD 86, an A/D converter 90 for converting analog data
produced by the CCD 86 to digital data, a data buffer 91 for
temporarily storing the data digitized by the A/D converter 90, and
a camera control circuit 92 for controlling the operation of the
cooled CCD camera 81. An opening formed between the dark box 82 and
the cooled CCD camera 81 is closed by a glass plate 95 and the
periphery of the cooled CCD camera 81 is formed with heat
dispersion fins 96 over substantially half its length for
dispersing heat.
[0332] A camera lens 97 disposed in the dark box 82 is mounted on
the front surface of the glass plate 95 disposed in the cooled CCD
camera 81.
[0333] FIG. 16 is a schematic vertical cross sectional view showing
the dark box 82.
[0334] As shown in FIG. 16, the dark box 82 is equipped with a
light emitting diode stimulating ray source 100 for emitting a
stimulating ray. The light emitting diode stimulating ray source
100 is provided with a filter 101 detachably mounted thereon and a
diffusion plate 102 mounted on the upper surface of the filter 101.
The stimulating ray is emitted via the diffusion plate 102 toward a
biochemical analysis unit (not shown) placed on the diffusion plate
102 so as to ensure that the biochemical analysis unit can be
uniformly irradiated with the stimulating ray. The filter 101 has a
property of cutting light components having a wavelength not close
to that of the stimulating ray and harmful to the stimulation of a
fluorescent substance and transmitting through only light
components having a wavelength in the vicinity of that of the
stimulating ray. A filter 102 for cutting light components having a
wavelength in the vicinity of that of the stimulating ray is
detachably provided on the front surface of the camera lens 97.
[0335] FIG. 17 is a block diagram of the personal computer 83 and
peripheral devices thereof.
[0336] As shown in FIG. 17, the personal computer 83 includes a CPU
110 for controlling the exposure of the cooled CCD camera 81, a
data transferring means 111 for reading the data produced by the
cooled CCD camera 81 from the data buffer 91, a storing means 112
for storing data, a data processing apparatus 113 for effecting
data processing on the digital data stored in the data storing
means 112, and a data displaying means 114 for displaying visual
data on the screen of the CRT 84 based on the digital data stored
in the data storing means 112. The light emitting diode stimulating
ray source 100 is controlled by a light source control means 115
and an instruction signal can be input via the CPU 110 to the light
source control means 115 through the keyboard 85. The CPU 110 is
constituted so as to output various signals to the camera
controlling circuit 93 of the cooled CCD camera 81.
[0337] The data producing system shown in FIGS. 14 to 17 is
constituted so as to detect chemiluminescent emission generated by
the contact of a labeling substance contained in the porous
material 4 charged in a number of through-holes 3 formed in the
biochemical analysis unit 1 and a chemiluminescent substrate, with
the CCD 86 of the cooled CCD camera 81 through a camera lens 97,
thereby producing chemiluminescence data, and irradiate the
biochemical analysis unit 1 with a stimulating ray emitted from the
light emitting diode stimulating ray source 100 and detect
fluorescence released from a fluorescent substance such as a
fluorescent dye contained in the porous material 4 charged in a
number of through-holes 3 formed in the biochemical analysis unit 1
upon being stimulated, with the CCD 86 of the cooled CCD camera 81
through a camera lens 97, thereby producing fluorescence data.
[0338] When chemiluminescence data are to be read out, the filter
102 is removed and while the light emitting diode stimulating ray
source 100 is kept off, the biochemical analysis unit 1 is placed
on the diffusion plate 103, which is releasing chemiluminescent
emission as a result of contact of a labeling substance contained
in the porous material 4 charged in a number of through-holes 3
formed in the biochemical analysis unit 1 and a chemiluminescent
substrate.
[0339] The lens focus is then adjusted by an operator using the
camera lens 97 and the dark box 92 is closed.
[0340] When an exposure start signal is input by the operator
through the keyboard 85, the exposure start signal is input through
the CPU 110 to the camera control circuit 92 of the cooled CCD
camera 81 so that the shutter 88 is opened by the camera control
circuit 92, whereby the exposure of the CCD 86 is started.
[0341] Chemiluminescent emission released from the biochemical
analysis unit 1 impinges on the light receiving surface of the CCD
86 of the cooled CCD camera 81 via the camera lens 97, thereby
forming an image on the light receiving surface. The CCD 86
receives light of the thus formed image and accumulates it in the
form of electric charges therein.
[0342] In this embodiment, since the substrate 2 of the biochemical
analysis unit 1 is formed of a metal capable of attenuating
radiation energy and light energy, it is possible to reliably
prevent chemiluminescent emission released from the labeling
substance from being scattered in the substrate 2 and mixed with
chemiluminescent emission released from a labeling substance
contained in porous material 4 charged in neighboring through-holes
3.
[0343] When a predetermined exposure time has passed, the CPU 110
outputs an exposure completion signal to the camera control circuit
92 of the cooled CCD camera 81.
[0344] When the camera controlling circuit 92 receives the exposure
completion signal from the CPU 110, it transfers analog data
accumulated in the CCD 86 in the form of electric charge to the A/D
converter 90 to cause the A/D converter 90 to digitize the data and
to temporarily store the thus digitized data in the data buffer
91.
[0345] At the same time, the CPU 110 outputs a data transfer signal
to the data transferring means 111 to cause it to read out the
digital data from the data buffer 91 of the cooled CCD camera 81
and to input them to the data storing means 112.
[0346] When the operator inputs a data producing signal through the
keyboard 85, the CPU 110 outputs the digital data stored in the
data storing means 112 to the data processing apparatus 113 and
causes the data processing apparatus 113 to effect data processing
on the digital data in accordance with the operator's instructions.
The CPU 110 then outputs a data display signal to the displaying
means 115 and causes the displaying means 115 to display
biochemical analysis data on the screen of the CRT 84 based on the
thus processed digital data.
[0347] On the other hand, when fluorescence data are to be read
out, the biochemical analysis unit 1 is first placed on the
diffusion plate 103.
[0348] The light emitting diode stimulating ray source 100 is then
turned on by the operator and the lens focus is adjusted using the
camera lens 97. The dark box 92 is then closed.
[0349] When the operator inputs an exposure start signal through
the keyboard 85, the light emitting diode stimulating ray source
100 is again turned on by the light source control means 115,
thereby emitting a stimulating ray toward the biochemical analysis
unit 1. At the same time, the exposure start signal is input via
the CPU 110 to the camera control circuit 92 of the cooled CCD
camera 81 and the shutter 89 is opened by the camera control
circuit 92, whereby the exposure of the CCD 86 is started.
[0350] The stimulating ray emitted from the light emitting diode
stimulating ray source 100 passes through the filter 101, whereby
light components of wavelengths not in the vicinity of that of the
stimulating ray are cut. The stimulating ray then passes through
the diffusion plate 103 to be made uniform light and the
biochemical analysis unit 1 is irradiated with the uniform
stimulating ray.
[0351] The fluorescence released from the biochemical analysis unit
1 impinges on the light receiving surface of the CCD 86 of the
cooled CCD camera 81 through the filter 102 and the camera lens 97
and forms an image thereon. The CCD 86 receives light of the thus
formed image and accumulates it in the form of electric charges
therein. Since light components of wavelength equal to the
stimulating ray wavelength are cut by the filter 102, only
fluorescence released from the fluorescent substance contained in
the porous material 4 charged in a number of the through-holes 3
formed in the biochemical analysis unit 1 is received by the CCD
86.
[0352] In this embodiment, since the substrate 2 of the biochemical
analysis unit 1 is formed of a metal capable of attenuating
radiation energy and light energy, it is possible to reliably
prevent fluorescence released from the fluorescent substance such
as a fluorescent dye from being scattered in the substrate 2 and
mixed with fluorescence released from a fluorescent substance
contained in porous material 4 charged in neighboring through-holes
3.
[0353] When a predetermined exposure time has passed, the CPU 110
outputs an exposure completion signal to the camera control circuit
92 of the cooled CCD camera 81.
[0354] When the camera controlling circuit 92 receives the exposure
completion signal from the CPU 110, it transfers analog data
accumulated in the CCD 86 in the form of electric charge to the A/D
converter 90 to cause the AID converter 90 to digitize the data and
to temporarily store the thus digitized data in the data buffer
91.
[0355] At the same time, the CPU 110 outputs a data transfer signal
to the data transferring means 111 to cause it to read out the
digital data from the data buffer 91 of the cooled CCD camera 81
and to input them to the data storing means 112.
[0356] When the operator inputs a data producing signal through the
keyboard 85, the CPU 110 outputs the digital data stored in the
data storing means 112 to the data processing apparatus 113 and
causes the data processing apparatus 113 to effect data processing
on the digital data in accordance with the operator's instructions.
The CPU 110 then outputs a data display signal to the displaying
means 115 and causes the displaying means 115 to display
biochemical analysis data on the screen of the CRT 84 based on the
thus processed digital data.
[0357] In this embodiment, the biochemical analysis unit 1 includes
the substrate 2 made of a metal capable of attenuating radiation
energy and light energy and having flexibility formed with a number
of the through-holes 3, and the porous material 4 is charged in the
through-holes 3. Specific binding substances such as a plurality of
cDNAs whose sequences are known but are different from each other
are spotted into in a number of the through-holes 3 of the
biochemical analysis unit 1 using the spotting device and are held
by the porous material 4.
[0358] A hybridization solution 9 containing a substance derived
from a living organism labeled with a radioactive labeling
substance, a substance derived from a living organism labeled with
a labeling substance which generates chemiluminescent emission when
it contacts a chemiluminescent substrate and a substance derived
from a living organism labeled with a fluorescent substance such as
a fluorescent dye is prepared and the biochemical analysis unit 1
is accommodated in the hybridization vessel 8 containing the thus
prepared hybridization solution 9, whereby specific binding
substances spotted in a number of the through-holes 3 charged with
porous material 4 are hybridized with the substances derived from a
living organism contained in the hybridization solution 9 and the
specific binding substances are selectively labeled with a
radioactive labeling substance, a fluorescent substance such as a
fluorescent dye and a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate.
[0359] When the stimulable phosphor sheet 10 is to be exposed to a
radioactive labeling substance, the stimulable phosphor sheet 10
including the support 11 on one side of which a number of dot-like
stimulable phosphor layer regions 12 are formed in the same pattern
as that of a number of through-holes 3 formed in the biochemical
analysis unit 1 is superposed on the biochemical analysis unit 1 in
such a manner that each of the dot-like stimulable phosphor layer
regions 12 formed in the stimulable phosphor sheet 10 is located in
one of the many through-holes 3 formed in the biochemical analysis
unit 1 and that the surface of each of the dot-like stimulable
phosphor layer regions 12 comes into close contact with the surface
of the porous material 4 charged in one of the through-holes 3,
thereby exposing a number of the dot-like stimulable phosphor layer
regions 12.
[0360] Therefore, according to this embodiment, since the substrate
2 of the biochemical analysis unit 1 is formed of a metal capable
of attenuating radiation energy and light energy, when the
stimulable phosphor sheet 10 is to be exposed, electron beams
released from the radioactive labeling substance are prevented from
being scattered in the substrate 2. Further, since each of a number
of dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 is located in one of the many
through-holes 3 formed in the biochemical analysis unit 1, the
electron beams released from the radioactive labeling substance are
prevented from being scattered in the dot-like stimulable phosphor
layer region 12 and advancing to dot-like stimulable phosphor layer
regions 12 located in neighboring through-holes. Accordingly, even
when the through-holes 3 are formed in the substrate 2 at high
density, it is possible to reliably expose a number of the dot-like
stimulable phosphor layer regions 12 formed in the stimulable
phosphor sheet 10 to only the radioactive labeling substance
contained in the porous material 4 charged in the corresponding
through-holes 3.
[0361] Furthermore, according to this embodiment, since the
substrate 2 of the biochemical analysis unit 1 is formed of a metal
capable of attenuating radiation energy and light energy,
fluorescence released from a fluorescent substance such as a
fluorescent dye as a result of being irradiated with a laser beam
24 or a stimulating ray emitted from the light emitting diode
stimulating ray source 100, can be reliably prevented from being
scattered in the substrate 2 and mixed with fluorescence released
from a fluorescent substance such as a fluorescent dye contained in
porous material 4 charged in neighboring through-holes 3.
Therefore, even when the through-holes 3 are formed in the
substrate 2 at high density, it is possible to reliably prevent
noise caused by the scattering of fluorescence from being generated
in biochemical analysis data produced by photoelectrically
detecting fluorescence and improve the quantitative accuracy of
biochemical analysis.
[0362] Furthermore, according to this embodiment, since the
substrate 2 of the biochemical analysis unit 1 is formed of a metal
capable of attenuating radiation energy and light energy,
chemiluminescent emission released a labeling substance by the
contact with a chemiluminescent substrate can be reliably prevented
from being scattered in the substrate 2 and mixed with
chemiluminescent emission released from a labeling substance
contained in porous material 4 charged in neighboring through-holes
3. Therefore, even when the through-holes 3 are formed in the
substrate 2 at high density, it is possible to reliably prevent
noise caused by the scattering of chemiluminescent emission from
being generated in biochemical analysis data produced by
photoelectrically detecting chemiluminescent emission and improve
the quantitative accuracy of biochemical analysis.
[0363] Further, according to this embodiment, since the substrate 2
of the biochemical analysis unit 1 is formed of a metal having
flexibility, the biochemical analysis unit 1 can be bent and
accommodated in the hybridization vessel 8 so as to be aligned with
the inner wall surface thereof, whereby specific binding substances
are selectively hybridized with substances derived from a living
organism. Therefore, hybridization can be accomplished using a
small amount of the hybridization solution 9.
[0364] Furthermore, according to this embodiment, since the
substrate 2 of the biochemical analysis unit 1 is formed of a
metal, it is hardly stretched and shrunk even when it is subjected
to liquid processing such as hybridization and, therefore, it is
possible to easily and accurately superpose the stimulable phosphor
sheet 10 on the biochemical analysis unit 1 so that each of the
dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 is located in one of the many
through-holes 3 formed in the biochemical analysis unit 1 and that
the surface of each of the dot-like stimulable phosphor layer
regions 12 comes into close contact with the surface of the porous
material 4 charged in one of the through-holes 3, thereby exposing
the dot-like stimulable phosphor layer regions 12.
[0365] FIG. 18 is a schematic vertical cross sectional view showing
another example of a dark box.
[0366] As shown in FIG. 18, at the bottom of a dark box 82
according to this embodiment, a vessel 131 containing a solution
130 containing a chemiluminescent substrate is provided and the
inner wall surface of the vessel 131 is formed with support members
132 for supporting the biochemical analysis unit 1.
[0367] When chemiluminescence data are to be read out, it is
preferable for improving the quantitative accuracy to keep the
labeling substance contained in the porous material 4 charged in a
number of the through-holes 3 of the biochemical analysis unit 1
and the chemiluminescent substrate constantly in contact with each
other so as to cause release of chemiluminescent emission having a
predetermined intensity. Therefore, in the dark box 82 according to
this embodiment, since the support members 132 enable the
biochemical analysis unit 1to be kept constantly in contact with
the solution 130 containing a chemiluminescent substrate
accommodated in the vessel 131 provided at the bottom of the dark
box 82 and chemiluminescent emission can be detected by the cooled
CCD camera 81, it is possible to markedly improve the quantitative
accuracy of biochemical analysis.
[0368] FIG. 19 is a schematic longitudinal cross sectional view
showing a biochemical analysis unit which is another embodiment of
the present invention.
[0369] As shown in FIG. 19, a biochemical analysis unit 1 includes
an absorptive substrate 140 formed of absorptive material such as
nylon-6 and is formed by closely contacting perforated plates 142,
142 made of a metal capable of attenuating radiation energy and
light energy and having flexibility and formed with a number of
through-holes 141.
[0370] Although not accurately shown in FIG. 19, in this
embodiment, similarly to the substrate 2 according to the previous
embodiment, about 10,000 through-holes 141 having a size of about
0.01 cm.sup.2 are regularly formed at a density of about 10,000 per
cm.sup.2 in the perforated plates 142, 142 and a number of
absorptive regions 144 are formed by the absorptive substrate 140
located in the through-holes 141.
[0371] In this embodiment, when biochemical analysis is to be
performed, specific binding substances such as a plurality of cDNAs
whose sequences are known but are different from each other are
spotted using the spotting device shown in FIG. 2 onto a number of
the absorptive regions 144 formed on the absorptive substrate 140
via a number of the through-holes 141 formed in the perforated
plates 142, 142.
[0372] When hybridization is to be performed, similarly to the
previous embodiment, the biochemical analysis unit 1 including a
number of the absorptive regions 144 into which specific binding
substances have been spotted is inserted into the hybridization
vessel 7, whereby the specific binding substances are selectively
hybridized with a substance derived from a living organism labeled
with a radioactive labeling substance, a substance derived from a
living organism labeled with a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate and a substance derived from a living organism labeled
with a fluorescent substance such as a fluorescent dye contained in
the hybridization solution 9.
[0373] As a result of the hybridization, fluorescence data of a
fluorescent substance such as a fluorescent dye and
chemiluminescence data of a substance derived from a living
organism labeled with a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate are recorded in the absorptive regions 144 formed on the
absorptive substrate 140.
[0374] When the stimulable phosphor sheet 10 is to be exposed to a
radioactive labeling substance, as shown in FIG. 4, the stimulable
phosphor sheet 10 formed with a number of dot-like stimulable
phosphor layer regions 12 is superposed on the biochemical analysis
unit 1. The dot-like stimulable phosphor layer regions 12 are
formed in the stimulable phosphor sheet 10 in the same regular
pattern as that of a number of the through-holes 141 formed in the
perforated plate 142.
[0375] FIG. 20 is a schematic cross-sectional view showing a method
for exposing a number of the dot-like stimulable phosphor layer
regions 12 formed on the stimulable phosphor sheet 10 to a
radioactive labeling substance contained in a number of the
absorptive regions 144 formed on the absorptive substrate 140.
[0376] As shown in FIG. 20, when the stimulable phosphor sheet 10
is to be exposed, the stimulable phosphor sheet 10 is superposed on
the biochemical analysis unit 1 in such a manner that each of the
dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 is located in one of the through-holes
3 formed in one of the perforated plates 142 of the biochemical
analysis unit 1 and that the surface of each of the dot-like
stimulable phosphor layer regions 12 comes into close contact with
the surface of the absorptive region 144.
[0377] Since specific binding substances are spotted using the
spotting device on the absorptive regions 144 formed on the
absorptive substrate 140 via the perforated plate 142, the surface
of each of the dot-like stimulable phosphor layer regions 12 is
accurately located in close contact with the spot-like regions
formed on the surface of the absorptive substrate 140 and
selectively labeled with a radioactive labeling substance.
[0378] In this manner, the surface of each of the dot-like
stimulable phosphor layer regions 12 is kept in close contact with
the surface of the absorptive regions 144 formed on the absorptive
substrate 140 for a predetermined time period, whereby a number of
the dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 are exposed to the radioactive
labeling substance contained in a number of the absorptive regions
144.
[0379] During the exposure operation, electron beams are released
from the radioactive labeling substance. However, since the
perforated plate 140 is formed of a metal capable of attenuating
radiation energy and light energy, electron beams released from the
radioactive labeling substance contained in the individual
absorptive regions 144 formed on the absorptive substrate 140 are
prevented from being mixed with electron beams released from the
radioactive labeling substance contained in neighboring absorptive
regions 144 formed on the absorptive substrate 140. Further, since
each of a number of dot-like stimulable phosphor layer regions 12
formed in the stimulable phosphor sheet 10 is located in one of the
through-holes 141 formed in the perforated plate 142, the electron
beams released from the radioactive labeling substance are reliably
prevented from being scattered in the dot-like stimulable phosphor
layer region 12 and advancing to the dot-like stimulable phosphor
layer regions 12 located in neighboring through-holes 141.
Therefore, it is possible to reliably expose a number of the
dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 to only the radioactive labeling
substance contained in the absorptive regions 144 formed on the
absorptive substrate 140 via corresponding through-holes 141 of the
perforated plate 142.
[0380] In this manner, radiation data of a radioactive labeling
substance are recorded in a number of the dot-like stimulable
phosphor layer regions 12 formed in the stimulable phosphor sheet
10.
[0381] Therefore, in the case where biochemical analysis data are
produced by irradiating the dot-like stimulable phosphor layer
regions 12 formed in the support 11 of the stimulable phosphor
sheet 10 at high density and exposed to a radioactive labeling
substance with a stimulating ray and photoelectrically detecting
stimulated emission released from the dot-like stimulable phosphor
layer regions 12, and substances derived from a living organism are
analyzed, it is possible to effectively prevent noise caused by the
scattering of electron beams released from the radioactive labeling
substance from being generated in biochemical analysis data.
[0382] On the other hand, chemiluminescence data of a labeling
substance which generates chemiluminescent emission when it
contacts a chemiluminescent substrate or fluorescence data of a
fluorescent substance such as a fluorescent dye recorded in a
number of the absorptive regions 144 formed on the absorptive
substrate 140 are read out by the data producing system shown in
FIGS. 14 to 17, thereby producing biochemical analysis data.
[0383] Since the perforate plate 142 formed with a number of the
through-holes 141 is located on the side of the camera lens 97 with
respect to the absorptive substrate 140 so as to be in close
contact with the absorptive substrate 140, chemiluminescent
emission released from a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate or fluorescence released from a fluorescent substance
contained in the individual absorptive regions 144 can be reliably
prevented from being mixed with chemiluminescent emission released
from the labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate or
fluorescence released from the fluorescent substance contained in
neighboring absorptive regions 144 formed on the absorptive
substrate 140 and, therefore, it is possible to effectively prevent
noise caused by the scattering of chemiluminescent emission or
fluorescence from being generated in biochemical analysis data
produced by photoelectrically detecting chemiluminescent emission
or fluorescence.
[0384] According to this embodiment, since the perforated plate 142
is made of a metal capable of attenuating radiation energy and
light energy, electron beams released from the radioactive labeling
substance contained in the individual absorptive regions 144 formed
on the absorptive substrate 140 can be reliably prevented from
being mixed with electron beams released from the radioactive
labeling substance contained in neighboring absorptive regions 144
formed on the absorptive substrate 140 and since each of a number
of dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 is located in one of the through-holes
141 formed in the biochemical analysis unit 1, electron beams
released from the radioactive labeling substance are prevented from
being scattered in the dot-like stimulable phosphor layer region 12
and advancing to the dot-like stimulable phosphor layer regions 12
located in neighboring through-holes 141. Accordingly, it is
possible to reliably expose a number of the dot-like stimulable
phosphor layer regions 12 formed in the stimulable phosphor sheet
10 to only the radioactive labeling substance contained in the
corresponding absorptive regions 144 formed on the absorptive
substrate 140 via the corresponding through-holes 141 of the
perforated plate 142. Therefore, in the case where biochemical
analysis data are produced by irradiating the dot-like stimulable
phosphor layer regions 12 formed in the support 11 of the
stimulable phosphor sheet 10 at high density and exposed to a
radioactive labeling substance with a stimulating ray and
photoelectrically detecting stimulated emission released from the
dot-like stimulable phosphor layer regions 12, and substances
derived from a living organism are analyzed, it is possible to
effectively prevent noise caused by the scattering of electron
beams released from the radioactive labeling substance from being
generated in biochemical analysis data.
[0385] On the other hand, according to this embodiment, since the
perforate plate 142 formed with a number of the through-holes 141
is located on the side of the camera lens 97 with respect to the
absorptive substrate 140 so as to be in close contact with the
absorptive substrate 140, chemiluminescent emission released from a
labeling substance which generates chemiluminescent emission when
it contacts a chemiluminescent substrate or fluorescence released
from a fluorescent substance contained the individual absorptive
regions 144 formed on the absorptive substrate 140 can be reliably
prevented from being mixed with chemiluminescent emission released
from the labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate or
fluorescence released from the fluorescent substance contained in
neighboring absorptive regions 144 formed on the absorptive
substrate 140 and, therefore, it is possible to effectively prevent
noise caused by the scattering of chemiluminescent emission or
fluorescence from being generated in biochemical analysis data
produced by photoelectrically detecting chemiluminescent emission
or fluorescence.
[0386] FIG. 21 is a schematic perspective view of a biochemical
analysis unit which is a further preferred embodiment of the
present invention.
[0387] A biochemical analysis unit 151 shown in FIG. 21 includes an
absorptive substrate 152 made of absorptive material such as
nylon-6 and a perforated plate 154 made of a metal such as aluminum
and formed with a number of substantially circular through-holes
153 regularly and at a high density, and the absorptive substrate
152 and the perforated plate 154 are in close contact with each
other.
[0388] Although not accurately shown in FIG. 21, similarly to the
biochemical analysis unit shown in FIG. 19, in this embodiment,
about 10,000 through-holes 153 having a size of about 0.01 mm.sup.2
are regularly formed at a density of about 5,000 per cm.sup.2 in
the perforated plate 154 and a number of absorptive regions 155 are
regularly formed by the absorptive substrate 152 in every
through-holes 153.
[0389] As shown in FIG. 21, the perforated plate 154 is formed with
a gripping portion 156 in this embodiment.
[0390] As shown in FIG. 21, the perforated plate 154 of the
biochemical analysis unit 151 according to this embodiment is
formed with a pair of positioning through-holes 157, 158 in the
vicinity of one side portion.
[0391] FIG. 22 is a schematic plan view showing another example of
a potting device.
[0392] As shown in FIG. 22, a spotting device according to this
embodiment is provided with a drive mechanism and the drive
mechanism of the spotting device is mounted on a frame 161 fixed to
a base plate 160 on which the biochemical analysis unit 151, onto
which specific binding substances such as cDNA are to be spotted,
is to be set.
[0393] As shown in FIG. 22, a sub-scanning pulse motor 162 and a
pair of rails 163, 163 are fixed on the frame 161 and a movable
base plate 164 is further provided so as to be movable along the
pair of rails 163, 163 in the sub-scanning direction indicated by
an arrow Y in FIG. 22.
[0394] The movable base plate 164 is formed with a threaded hole
(not shown) and a threaded rod 165 rotated by the sub-scanning
pulse motor 162 is engaged with the inside of the hole.
[0395] A main scanning pulse motor 166 is provided on the movable
base plate 164. The main scanning pulse motor 165 is adapted for
intermittently driving an endless belt 167 at a predetermined
pitch.
[0396] The spotting head 5 of the spotting device is fixed to the
endless belt 167 and when the endless belt 167 is driven by the
main scanning pulse motor 166, the spotting head 5 is moved in the
main scanning direction indicated by an arrow X in FIG. 22.
[0397] Although not shown in FIG. 22, the spotting head 5 includes
an injector 6 for ejecting a solution of specific binding
substances toward the biochemical analysis unit 151 and a CCD
camera 7.
[0398] In FIG. 22, the reference numeral 168 designates a linear
encoder for detecting the position of the spotting head 5 in the
main scanning direction and the reference numeral 169 designates
slits of the linear encoder 168.
[0399] As shown in FIG. 22, two positioning pins 177, 178 are
uprightly formed on the base plate 160 of the spotting device at
positions corresponding to those of the two positioning
through-holes 157, 158 formed in the perforated plate 154 of the
biochemical analysis unit 151. Placement of the biochemical
analysis unit 151 at a substantially constant position on the base
plate 160 of the spotting device is ensured by placing the
biochemical analysis unit 151 on the base plate 160 of the spotting
device so that the two positioning pins 177, 178 formed on the base
plate 160 of the spotting device are inserted into the
corresponding positioning through-holes 157, 158.
[0400] FIG. 23 is a block diagram showing a control system, an
input system, a drive system and a detection system of the spotting
device.
[0401] As shown in FIG. 23, the control system of the spotting
device includes a control unit 180 for controlling the whole
operation of the spotting device and the input system of the
spotting device includes a keyboard 181.
[0402] The drive system of the spotting device includes a main
scanning pulse motor 166 and a sub-scanning pulse motor 162, and
the detection system of the spotting device includes a linear
encoder 166 for detecting the position of the spotting head 5 in
the main scanning direction, a rotary encoder 170 for detecting the
amount of rotation of the rod 165 and a CCD camera 7.
[0403] Specific binding substances such as cDNA are spotted by the
thus constituted spotting device onto a number of absorptive
regions 155 formed in the biochemical analysis unit 151 according
to this embodiment in the following manner.
[0404] The biochemical analysis unit 151 is first placed on the
base plate 160 of the spotting device so that the two positioning
pins 177, 178 formed on the base plate 160 of the spotting device
enter the corresponding positioning through-holes 157, 158.
[0405] In this embodiment, it is ensured in this manner that the
biochemical analysis unit 151 is placed at a substantially constant
position on the base plate 160 of the spotting device. However,
since each of the absorptive regions has a size of only about 0.01
mm.sup.2 in this embodiment, it cannot be ensured that the centers
of the absorptive regions 155 of the biochemical analysis unit 151
thus placed on the base plate 160 are exactly aligned with the main
scanning direction and the sub-scanning direction of the spotting
head 5.
[0406] Therefore, the spotting device according to this embodiment
is constituted so as to detect in advance the relative positional
relationship between the position of the biochemical analysis unit
151 placed on the base plate 160 and the positions of the spotting
head 5 to be moved in main scanning direction and the sub-scanning
direction, and to move the spotting head 5 by the main scanning
pulse motor 166 and the sub-scanning pulse motor 162 so that the
injector 6 can accurately spot specific binding substances onto the
absorptive regions 155.
[0407] When a spotting operation start signal is input by a user
through the keyboard 181 and the spotting operation start signal is
input to the control unit 180, the control unit 180 outputs a drive
signal to the main scanning pulse motor 166, thereby moving the
spotting head 5 located at a reference position in the main
scanning direction indicated by an arrow X in FIG. 22 and then
outputs a drive signal to the sub-scanning pulse motor 162, thereby
moving the spotting head 5 in the sub-scanning direction indicated
by an arrow Y in FIG. 22.
[0408] While the spotting head 5 is being moved in the main
scanning direction indicated by an arrow X and in the main scanning
direction indicated by an arrow X, the control unit 180 monitors
detection signals input from the CCD camera 7, thereby detecting
four corner portions of the biochemical analysis unit 151,
calculates coordinate values of the four corner portions of the
biochemical analysis unit 151 in a coordinate system whose origin
is the reference position of the spotting head 5, and stores them
in a memory (not shown).
[0409] When the four corner portions of the biochemical analysis
unit 151 are detected and the coordinate values thereof are stored
in the memory, the control unit 180 calculates coordinate values of
the respective absorptive regions 155 formed in the biochemical
analysis unit 151 based on the coordinate values of the four corner
portions of the biochemical analysis unit 151 in the coordinate
system whose origin is the reference position of the spotting head
5 and stores them in the memory (not shown).
[0410] When the coordinate values of the respective absorptive
regions 155 formed in the biochemical analysis unit 151 have been
calculated in the coordinate system whose origin is the reference
position of the spotting head 5 and stored in the memory, the
control unit 180 outputs drive signals to the main scanning pulse
motor 166 and the sub-scanning pulse motor 162, thereby returning
the spotting head 5 to the original reference position.
[0411] In the case where specific binding substances ejected from
the injector 6 of the spotting head 5 are accurately spotted at the
position the tip end portion of the injector 6 faces, specific
binding substances can be accurately spotted onto the respective
absorptive regions 155 formed in the biochemical analysis unit 151
by ejecting specific binding substances from the injector 6 of the
spotting head 5 in the above-described manner based on the
coordinate values of the respective absorptive regions 155 of the
biochemical analysis unit 151 in the coordinate system determined
so that the reference position of the spotting head 5 is the origin
thereof. However, in the case where specific binding substances
ejected from the injector 6 of the spotting head 5 are spotted at a
position deviating in the X direction and/or the Y direction from
the position the tip end portion of the injector 6 faces, even if
specific binding substances are ejected from the injector 6 of the
spotting head 5 in the above-described manner based on the
coordinate values of the respective absorptive regions 155 of the
biochemical analysis unit 151 in the coordinate system determined
so that the reference position of the spotting head 5 is the origin
thereof, it is impossible to accurately spot specific binding
substances onto the respective absorptive regions 155 formed in the
biochemical analysis unit 151.
[0412] In view of the above, in this embodiment, specific binding
substances are ejected from the injector 6 of the spotting head 5
returned to the reference position thereof toward the surface of
the biochemical analysis unit 151, whereby the position of the thus
spotted specific binding substances is detected by the CCD camera
7, and amounts of deviation from the position the tip end portion
of the injector 6 faces in the X direction and the Y direction are
calculated by the control unit 180 based on a detection signal of
the CCD camera 7 and the calculated amounts of deviation are stored
in the memory.
[0413] More specifically, as shown in FIG. 24, specific binding
substances are ejected from the injector 6 of the spotting head 5
located at the reference position thereof toward the surface of the
biochemical analysis unit 151 and the position of the thus spotted
specific binding substances is detected by the CCD camera 7. The
control unit 180 then calculates an amount of deviation .delta.x in
the X direction and an amount of deviation .delta.y in the Y
direction from the position O the tip end portion of the injector 6
faces based on a detection signal from the CCD camera and stores
them in the memory.
[0414] Since the amount of deviation .delta.x in the X direction
and the amount of deviation .delta.y in the Y direction of the
position of spotted specific binding substances from the position O
the tip end portion of the injector 6 faces are inherent in the
respective injector 6 of the spotting head 5, it follows that the
position of spotted specific binding substances ejected from the
injector 6 toward the surface of the biochemical analysis unit 151
when the spotting head 5 is located at a position other than the
reference position thereof deviates from the position O the tip end
portion of the injector 6 faces by .delta.x in the X direction and
by .delta.y in the Y direction.
[0415] Then, based on the coordinate values of the four corner
portions of the biochemical analysis unit 151 and the coordinate
values of the respective absorptive regions 155 formed in the
biochemical analysis unit 151 in the coordinate system whose origin
is the reference position of the spotting head 5 and the amount of
deviation .delta.x in the X direction and the amount of deviation
.delta.y in the Y direction of the position of spotted specific
binding substances, the control unit 180 calculates drive pulses to
be sent to the main scanning pulse motor 166 and the sub-scanning
pulse motor 162 in order to move the spotting head 5 to positions
where the tip end portion of the injector 6 of the spotting head 5
faces the respective absorptive regions 155 and stores driving
pulse data in the memory.
[0416] In this embodiment, a number of absorptive regions 155 of
the biochemical analysis unit 151 are formed one in every
through-hole 153 regularly formed in the perforated plate 154.
Therefore, the drive pulses to be sent to the main scanning pulse
motor 166 and the sub-scanning pulse motor 162 in order to move the
spotting head 5 to a position where the tip end portion of the
injector 6 of the spotting device faces the third absorptive region
155 to which specific binding substances are to be spotted and from
there to each successive position where the tip end portion of the
injector 6 of the spotting device faces an absorptive region 155 to
which specific binding substances are to be spotted are equal to
the drive pulses to be sent to the main scanning pulse motor 166
and the sub-scanning pulse motor 162 in order to move the spotting
head 5 from the position where the tip end portion of the injector
6 of the spotting device faces the first absorptive region 155 to
which specific binding substances are to be spotted to the position
where the tip end portion of the injector 6 of the spotting device
faces the second absorptive region 155 to which specific binding
substances are to be spotted. Accordingly, it is sufficient to
calculate drive pulses to be sent to the main scanning pulse motor
166 and the sub-scanning pulse motor 162 in order to move the
spotting head 5 from the reference position of the spotting head 5
to the position where the tip end portion of the injector 6 of the
spotting device faces the first absorptive region 155 to which
specific binding substances are to be spotted, calculate drive
pulses to be sent to the main scanning pulse motor 166 and the
sub-scanning pulse motor 162 in order to move the spotting head 5
from the position where the tip end portion of the injector 6 of
the spotting device faces the first absorptive region 155 to which
specific binding substances are to be spotted to the position where
the tip end portion of the injector 6 of the spotting device faces
the second absorptive region 155 to which specific binding
substances are to be spotted, and store the calculated drive pulse
data in the memory.
[0417] When drive pulses to be sent to the main scanning pulse
motor 166 and the sub-scanning pulse motor 162 in order to move the
spotting head 5 to the position where the tip end portion of the
injector 6 of the spotting device faces the respective absorptive
regions 155 have been calculated and drive pulse data have been
stored in the memory, the control unit 180 sends predetermined
drive pulses to the main scanning pulse motor 166 and the
sub-scanning pulse motor 162 based on the drive pulse data stored
in the memory, thereby intermittently moving the spotting head 5.
When the spotting head 5 has reached the positions where it faces
the respective absorptive regions 155 formed in the biochemical
analysis unit 151, the control unit 180 outputs drive stop signals
to the main scanning pulse motor 166 and the sub-scanning pulse
motor 162, thereby stopping the spotting head 5 and outputs a spot
signal to the injector 6 of the spotting head 5, thereby causing it
to spot specific binding substances.
[0418] In the case where the spotting head 5 is to be moved to the
position where the tip end portion of the injector 6 of the
spotting head 5 faces the second or a subsequent absorptive region
155 to which specific binding substances are to be spotted, the
spotting head 5 is moved at predetermined pitches in the main
scanning direction indicated by the arrow X and in the sub-scanning
direction indicated by the arrow Y.
[0419] The spotting head 5 is intermittently moved by the main
scanning pulse motor 166 and the sub-scanning pulse motor 162 in
this manner and specific binding substances are successively
spotted onto the absorptive regions 155 formed in the biochemical
analysis unit 151.
[0420] According to this embodiment, the position of the
biochemical analysis unit 151 with respect to the spotting head 5
is detected in advance by the CCD camera 7, the coordinate values
of the respective absorptive regions 155 are calculated by the
control unit 180 using the reference position of the spotting head
5 as the origin of the coordinate system, and the calculated
coordinate values are stored in the memory. Specific binding
substances are ejected toward the surface of the biochemical
analysis unit 151 from the injector 6 of the spotting head 5
located at the reference position thereof and the position where
the specific binding substances are spotted is detected by the CCD
camera 7, whereby the amount of deviation .delta.x in the X
direction and the amount of deviation .delta.y in the Y direction
of the position of the spotted specific binding substances from the
position O where the tip end portion of the injector 6 faces are
calculated by the control unit 180 and stored in the memory. The
control unit 180 calculates, based on these data, drive pulses to
be sent to the main scanning pulse motor 166 and the sub-scanning
pulse motor 162 in order to move the spotting head 5 to the
position where the tip end portion of the injector 6 of the
spotting device faces the respective absorptive regions 155 and
stores the drive pulse data in the memory. When specific binding
substances are to be spotted, the control unit 180 sends
predetermined drive pulses to the main scanning pulse motor 166 and
the sub-scanning pulse motor 162 based on the drive pulse data
stored in the memory. When the spotting head 5 has reached the
positions where it faces the respective absorptive regions 155
formed in the biochemical analysis unit 151, the control unit 180
outputs drive stop signals to the main scanning pulse motor 166 and
the sub-scanning pulse motor 162, thereby stopping the spotting
head 5 and outputs a spot signal to the injector 6 of the spotting
head 5, thereby causing it to specific binding substances.
Therefore, even when the biochemical analysis unit 151 is not
accurately set on the base plate 160 so as to have a predetermined
positional relationship with the spotting device, specific binding
substances such as cDNA can be reliably spotted in the respective
absorptive regions 155 formed in the biochemical analysis unit
151.
[0421] Further, according to this embodiment, since the biochemical
analysis unit 151 includes the perforated plate 154 made of
aluminum and the perforated plate 154 is formed with the gripping
portion 156, the biochemical analysis unit 151 can be very easily
handled when specific binding substances are spotted, during
hybridization or during exposure operation.
[0422] Furthermore, according to this embodiment, the biochemical
analysis unit 151 and the stimulable phosphor sheet 10 can be
desirably positioned for exposure utilizing the two positioning
through-holes 157, 158 formed in the vicinity of one side portion
of the perforated plate 154.
[0423] FIG. 25 is a schematic perspective view of a biochemical
analysis unit which is a further preferred embodiment of the
present invention.
[0424] Similarly to the biochemical analysis unit 1 shown in FIG.
1, a biochemical analysis unit 191 includes a substrate 192 made of
aluminum and formed with a number of substantially circular
through-holes 193 regularly and at a high density, and a number of
absorptive regions 194 are formed by charging absorptive material
such as nylon-6 in every through-hole 193.
[0425] The biochemical analysis unit 191 further includes a frame
member 196 including a pair of plate-like members 195, 195 and
adapted for holding the peripheral portion of the substrate 192
therebetween and carrying the substrate 192. The plate-like members
195, 195 are formed of rigid material.
[0426] Similarly to the embodiment shown in FIG. 21, as shown in
FIG. 25, the frame member 196 is formed with two positioning
through-hole 197, 198.
[0427] According to this embodiment, since the substrate 192 of the
biochemical analysis unit 191 is held between the frame member 196
formed of rigid material, the biochemical analysis unit 191 can be
very easily handled when specific binding substances are spotted,
during hybridization or during exposure operation.
[0428] Furthermore, according to this embodiment, since the frame
member 196 of the biochemical analysis unit 191 is formed with the
two positioning through-holes 197, 198, specific binding substances
can be accurately spotted onto a number of the absorptive regions
194 utilizing the spotting device shown in FIG. 22.
[0429] Moreover, according to this embodiment, since the substrate
192 of the biochemical analysis unit 191 is held between the frame
member 196 formed of rigid material, the biochemical analysis unit
191 and the stimulable phosphor sheet 10 can be desirably
positioned for exposure utilizing the frame member 196 formed of
rigid material.
[0430] The present invention has thus been shown and described with
reference to specific embodiments. However, it should be noted that
the present invention is in no way limited to the details of the
described arrangements but changes and modifications may be made
without departing from the scope of the appended claims.
[0431] For example, in the above-described embodiments, as specific
binding substances, cDNAs each of which has a known base sequence
and is different from the others are used. However, specific
binding substances usable in the present invention are not limited
to cDNAs but all specific binding substances capable of
specifically binding with a substance derived from a living
organism such as a hormone, tumor marker, enzyme, antibody,
antigen, abzyme, other protein, a nuclear acid, cDNA, DNA, RNA or
the like and whose sequence, base length, composition and the like
are known, can be employed in the present invention as a specific
binding substance.
[0432] Further, in the above-described embodiments, although the
substrate 2 or the perforated plate 142 is made of a metal, it is
sufficient to make the substrate 2 or the perforated plate 142 of a
material capable of attenuating radiation energy and light energy.
Therefore, the invention is not limited to forming the substrate 2
or the perforated plate 142 of a metal and the substrate 2 and the
perforated plate 142 may instead be formed of a ceramic material or
a plastic material.
[0433] Furthermore, in the above-described embodiments, although
the substrate 2 or the perforated plate 142 has flexibility, it is
not absolutely necessary to form the substrate 2 or the perforated
plate 142 so as to be flexible.
[0434] Moreover, in the above-described embodiments, the substrate
2 or the perforated plate 142 of the biochemical analysis unit 1 is
made of a material capable of attenuating radiation energy and
light energy. However, in the case where biochemical analysis is
performed only by detecting radiation data recorded in the dot-like
stimulable phosphor layer regions 12 of the stimulable phosphor
sheet 10, the substrate 2 or the perforated plate 142 may be made
of a material capable of transmitting light but attenuating
radiation energy. On the other hand, in the case where biochemical
analysis is performed only by detecting chemiluminescence data or
fluorescence data, the substrate 2 or the perforated plate 142 may
be made of a material capable of transmitting radiation but
attenuating light energy. Therefore, it is not absolutely necessary
to form the substrate 2 or the perforated plate 142 of a material
capable of attenuating radiation energy and light energy.
[0435] Further, a porous material is charged in a number of the
through-holes 3 formed in the substrate 2 to form the absorptive
regions 4 in the embodiment shown in FIGS. 1 to 18. However, it is
possible to form a number of recesses in the substrate 2, instead
of the through-holes 3, and to charge or embed a porous material to
form the absorptive regions 4.
[0436] Furthermore, in the above-described embodiments, although
about 10,000 of the through-holes 3 or through-holes 143 having a
size of about 0.01 cm.sup.2 are regularly formed in the substrate 2
or the perforated plate 142 at a density of about 10,000/cm.sup.2,
the number or size of the through-holes 3 or through-holes 143 may
be arbitrarily selected in accordance with the purposes.
Preferably, 10 or more of the through-holes 3 or through-holes 143
having a size of 5 cm.sup.2 or less are formed in the substrate 2
or the perforated plate 142 at a density of 10/cm.sup.2 or
less.
[0437] Moreover, in the above-described embodiments, although about
10,000 of the through-holes 3 or through-holes 143 having a size of
about 0.01 cm.sup.2 are regularly formed in the substrate 2 or the
perforated plate 142 at a density of about 10,000/cm.sup.2, it is
not absolutely necessary to regularly form the through-holes 3 or
through-holes 143 in the substrate 2 or the perforated plate
142.
[0438] Further, in the above-described embodiments, a hybridization
solution 9 containing a substance derived from a living organism
labeled with a radioactive labeling substance, a substance derived
from a living organism labeled with a labeling substance which
generates chemiluminescent emission when it contacts a
chemiluminescent substrate and a substance derived from a living
organism labeled with a fluorescent substance such as a fluorescent
dye is prepared and hybridized with specific binding substances
spotted in the absorptive region 4. However, it is not absolutely
necessary for substances derived from a living organism to be
labeled with a radioactive labeling substance, a fluorescent
substance and a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate and it is
sufficient for substances derived from a living organism to be
labeled with at least one kind of a labeling substance selected
from a group consisting of a radioactive labeling substance, a
fluorescent substance and a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate.
[0439] Furthermore, in the above-described embodiments, specific
binding substances are hybridized with substances derived from a
living organism labeled with a radioactive labeling substance, a
fluorescent substance and a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate. However, it is not absolutely necessary to hybridize
substances derived from a living organism with specific binding
substances and substances derived from a living organism may be
specifically bound with specific binding substances by means of
antigen-antibody reaction, receptor-ligand reaction or the like
instead of hybridization.
[0440] Moreover, in the above-described embodiments, a number of
the dot-like stimulable phosphor layer regions 12 are formed on one
surface of the support 11 of the stimulable phosphor sheet 10 in
the same pattern as that of a number of the through-holes 3 formed
in the biochemical analysis unit 1 of the same pattern as that of a
number of the through-holes 141 formed in the perforated plate 142.
However, it is not absolutely necessary to form the dot-like
stimulable phosphor layer regions 12 and a stimulable phosphor
layer may be uniformly formed on one surface of the support 11 of
the stimulable phosphor sheet 10.
[0441] Further, the dot-like stimulable phosphor layer regions 12
are exposed to a radioactive labeling substance by superposing the
biochemical analysis unit 1 and the stimulable phosphor sheet 10 so
that the absorption regions 4 formed in the through-holes 4 of the
biochemical analysis unit 1 and the dot-like stimulable phosphor
layer regions 12 of the stimulable phosphor sheet 10 are in close
contact with each other in the embodiment shown in FIGS. 1 to 18
and the dot-like stimulable phosphor layer regions 12 are exposed
to a radioactive labeling substance by superposing the biochemical
analysis unit 1 and the stimulable phosphor sheet 10 so that the
absorption regions 144 formed on the absorptive substrate 140 of
the biochemical analysis unit 1 and the dot-like stimulable
phosphor layer regions 12 of the stimulable phosphor sheet 10 are
in close contact with each other in the embodiment shown in FIGS.
19 and 20. However, it is sufficient for the dot-like stimulable
phosphor layer regions 12 to be exposed to a radioactive labeling
substance by superposing the biochemical analysis unit 1 and the
stimulable phosphor sheet 10 so that the dot-like stimulable
phosphor layer regions 12 of the stimulable phosphor sheet 10 face
the absorption regions 4 formed in the through-holes 4 of the
biochemical analysis unit 1 or the absorptive substrate 140 of the
biochemical analysis unit 1 and it is not absolutely necessary to
expose the dot-like stimulable phosphor layer regions 12 to a
radioactive labeling substance by keeping the dot-like stimulable
phosphor layer regions 12 of the stimulable phosphor sheet 10 in
close contact with the absorption regions 4 formed in the
through-holes 4 of the biochemical analysis unit 1 or the
absorptive regions 144 formed on the absorptive substrate 140 of
the biochemical analysis unit 1.
[0442] Moreover, in the above-described embodiments, although a
number of the dot-like stimulable phosphor layer regions 12 of the
stimulable phosphor sheet 10 are formed on the surface of the
support 11, it is not absolutely necessary to form a number of the
dot-like stimulable phosphor layer regions 12 on the surface of the
support 11. A number of dot-like stimulable phosphor layer regions
12 may be formed by forming a number of through-holes in the
support 11 and charging or embedding stimulable phosphor into a
number of the through-holes or forming a number of recesses in the
support 11 and charging or embedding stimulable phosphor into a
number of the recesses.
[0443] Furthermore, in the above-described embodiments, although a
number of the dot-like stimulable phosphor layer regions 12 of the
stimulable phosphor sheet 10 are formed so that the surface thereof
is located above the surface of the support 11, a number of the
dot-like stimulable phosphor layer regions 12 may be formed so that
the surface thereof is flush with the surface of the support 11 or
that the surface thereof is located below the surface of the
support 11.
[0444] Moreover, in the above-described embodiments, although the
support 11 of the stimulable phosphor sheet 10 is made of
stainless, it is sufficient for the support 11 to be made of a
material capable of attenuating radiation energy and light energy
and the support 11 can be formed of either inorganic compound
material or organic compound material and is preferably formed of
metal material, ceramic material or plastic material Illustrative
examples of inorganic compound materials include metals such as
gold, silver, copper, zinc, aluminum, titanium, tantalum, chromium,
steel, nickel cobalt, lead, tin, selenium and the like; alloys such
as brass, stainless, bronze and the like; silicon materials such as
silicon, amorphous silicon, glass, quartz, silicon carbide, silicon
nitride and the like; metal oxides such as aluminum oxide,
magnesium oxide, zirconium oxide and the like; and inorganic salts
such as tungsten carbide, calcium carbide, calcium sulfate, hydroxy
apatite, gallium arsenide and the like. High molecular compounds
are preferably used as organic compound material and illustrative
examples thereof include polyolefins such as polyethylene,
polypropylene and the like; acrylic resins such as polymethyl
methacrylate, polybutylacrylate/polymethyl methacrylate copolymer
and the like; polyacrylonitrile; polyvinyl chloride; polyvinylidene
chloride; polyvinylidene fluoride; polytetrafluoroethylene;
polychlorotrifuluoroethylene; polycarbonate; polyesters such as
polyethylene naphthalate, polyethylene terephthalate and the like;
nylons such as nylon-6, nylon-6, 6, nylon-4, 10 and the like;
polyimide; polysulfone; polyphenylene sulfide; silicon resins such
as polydiphenyl siloxane and the like; phenol resins such as
novolac and the like; epoxy resin; polyurethane; polystyrene,
butadiene-styrene copolymer; polysaccharides such as cellulose,
acetyl cellulose, nitrocellulose, starch, calcium alginate,
hydroxypropyl methyl cellulose and the like; chitin; chitosan;
urushi (Japanese lacquer); polyamides such as gelatin, collagen,
keratin and the like; and copolymers of these high molecular
materials
[0445] Further, the biochemical analysis unit 1 is constituted in
the embodiment shown in FIGS. 19 and 20 by bringing the perforated
plates 142, 142 formed with a number of the through-holes 141 into
close contact with the both sides of the absorptive substrate 140
formed of an absorptive material such as nylon-6. However, it is
not absolutely necessary to constitute the biochemical analysis
unit 1 by abutting the perforated plates 142, 142 against both
sides of the absorptive substrate 140 and the biochemical analysis
unit 1 may be constituted by abutting the perforated plate 142
formed with a number of the through-holes 141 against only one
surface of the absorptive substrate 140.
[0446] Furthermore, in the above-described embodiments, biochemical
analysis data are produced by reading radiation data of a
radioactive labeling substance recorded in a number of the dot-like
stimulable phosphor layer regions 12 formed in the stimulable
phosphor sheet 10 and fluorescence data of a fluorescent substance
such as a fluorescent dye recorded in the absorptive regions 4
formed in the through-holes 3 of the biochemical analysis unit 1
using the scanner shown in FIGS. 6 to 13. However, it is not
absolutely necessary to produce biochemical analysis data by
reading radiation data of a radioactive labeling substance and
fluorescence data of a fluorescent substance using a single scanner
and biochemical analysis data may be produced by reading radiation
data of a radioactive labeling substance and fluorescence data of a
fluorescent substance using separate scanners.
[0447] Moreover, in the above-described embodiments, biochemical
analysis data are produced by reading radiation data of a
radioactive labeling substance recorded in a number of the dot-like
stimulable phosphor layer regions 12 formed in the stimulable
phosphor sheet 10 and fluorescence data of a fluorescent substance
such as a fluorescent dye recorded in the absorptive regions 4
formed in the through-holes 3 of the biochemical analysis unit 1
using the scanner shown in FIGS. 6 to 13. However, it is not
absolutely necessary to read radiation data of a radioactive
labeling substance using the scanner shown in FIGS. 6 to 13 and any
scanner constituted so as to scan and stimulate a number the
dot-like stimulable phosphor layer regions 12 with a laser beam 24
may be used for reading radiation data of a radioactive labeling
substance.
[0448] Further, although the scanner shown in FIGS. 6 to 13
includes the first laser stimulating ray source 1, the second laser
stimulating ray source 2 and the third laser stimulating ray source
3, it is not absolutely necessary for the scanner to include three
laser stimulating ray sources.
[0449] Furthermore, in the above-described embodiments, biochemical
analysis data are produced by reading chemiluminescence data of a
labeling substance which generates chemiluminescent emission when
it contacts a chemiluminescent substrate recorded in the absorptive
regions 4 formed in the through-holes 3 of the biochemical analysis
unit 1 using the data producing system which can also read
fluorescence data. However, it is not absolutely necessary to
produce biochemical analysis data by reading chemiluminescence data
using the data producing system which can also read fluorescence
data and in the case where only chemiluminescence data of a
labeling substance which generates chemiluminescent emission when
it contacts a chemiluminescent substrate recorded in the absorptive
regions 4 formed in the through-holes 3 of the biochemical analysis
unit 1 are read, the light emitting diode stimulating ray source
100, the filter 101, the filter 102 and the diffusion plate 102 can
be omitted from the data producing system.
[0450] Moreover, in the above-described embodiments, all of the
dot-like stimulable phosphor layer regions 12 formed in the
stimulable phosphor sheet 10 or the entire surface of the
biochemical analysis unit 1 is scanned with a laser beam 24 to
excite stimulable phosphor or a fluorescent substance such as a
fluorescent dye by moving the optical head 35 using a scanning
mechanism in the X direction and the Y direction in FIG. 12.
However, all of the dot-like stimulable phosphor layer regions 12
formed in the stimulable phosphor sheet 10 or the entire surface of
the biochemical analysis unit 1 can be scanned with a laser beam 24
to excite stimulable phosphor or a fluorescent substance such as a
fluorescent dye by moving the stage 40 in the X direction and the Y
direction in FIG. 12, while holding the stage 40 stationary.
Further, the optical head 35 may be moved in one of the X direction
and the Y direction in FIG. 12, while the stage 40 is moved in the
other direction.
[0451] Furthermore, although the perforated mirror 34 formed with
the hole 33 is used in the scanner shown in FIGS. 6 to 13, the
mirror can be formed with a coating capable of transmitting the
laser beam 24 instead of the hole 33.
[0452] Moreover, the photomultiplier 50 is employed as a light
detector to photoelectrically detect fluorescent light or
stimulated emission in the scanner shown in FIGS. 6 to 13. However,
it is sufficient for the light detector used in the present
invention to be able to photoelectrically detect fluorescent light
or stimulated emission and it is possible to employ a light
detector such as a line CCD or a two-dimensional CCD instead of the
photomultiplier 50.
[0453] Further, in the above-described embodiments, specific
binding substances such as cDNAs are spotted using the spotting
device including an injector 6 and a CCD camera 7 so that when the
tip end portion of the injector 6 and the center of the
through-hole 3 or the through-hole 141 into which a specific
binding substance is to be spotted are determined to coincide with
each other as a result of viewing them using the CCD camera 7, the
specific binding substance such as cDNA is spotted from the
injector 6. However, specific binding substances such as cDNAs can
be spotted by detecting the positional relationship between the
through-holes 3 or the through-holes 141 formed in the biochemical
analysis unit 1 and the tip end portion of the injector 6 in
advance and two-dimensionally moving the biochemical analysis unit
1 or the tip end portion of the injector 6 so that the tip end
portion of the injector 6 coincides with each of the through-holes
3 or the through-holes 141.
[0454] Furthermore, although the spotting head 5 of the spotting
device includes the injector 6 for injecting a solution of specific
binding substances toward the biochemical analysis unit 1, 151 and
the CCD camera 7 in the above described embodiments, the spotting
head 5 may include, instead of the injector 6, a spotting pin for
spotting specific binding substances onto the biochemical analysis
unit 1, 151.
[0455] Moreover, although the spotting head 5 of the spotting
device includes the CCD camera 7, it is not absolutely necessary
for the spotting head 5 to include the CCD camera 7 and other
solid-state imaging devices such as a CID (charge injection
device), a PDA (photodiode array), a MOS type imaging device and
the like may be used.
[0456] Further, in the embodiment shown in FIGS. 21 to 24, although
four corner portions of the biochemical analysis unit 151 are
detected and the coordinate values thereof are calculated using the
reference position of the spotting head 5 as the origin of the
coordinate system, it is sufficient to determine the relative
positional relationship between the biochemical analysis unit 151
and the spotting head 5 of the spotting device and it is not
absolutely necessary to detect four corner portions of the
biochemical analysis unit 151 and calculate the coordinate values
thereof. It is possible to detect diagonally opposite corner
portions of the biochemical analysis unit 151, calculate the
coordinate values thereof using the reference position of the
spotting head 5 as the origin of the coordinate system, calculate
drive pulses to be sent to the main scanning pulse motor 166 and
the sub-scanning pulse motor 162, and move the spotting head 5.
[0457] Furthermore, in the embodiment shown in FIGS. 21 to 24,
setting of the biochemical analysis unit 151 at a substantially
constant position on the base plate 160 is ensured by placing the
biochemical analysis unit 151 on the base plate 160 so that two
positioning pins 177, 178 formed on the base plate 160 of the
spotting device are inserted into two positioning through-holes
157, 158 of the biochemical analysis unit 151. Alternatively, three
or more positioning pins may be formed on the base plate 160 and
corresponding through-holes be formed in the biochemical analysis
unit 151. Further, exact positioning of the biochemical analysis
unit 151 on the base plate 160 of the spotting device may be
ensured, not by providing the two positioning pins 157, 158, but
instead by forming, for instance, a pair of guides having side
portions perpendicular to each other on the surface of the base
plate 160 of the spotting device and abutting side surfaces
adjacent to the corner portion of the biochemical analysis unit 151
against each of the guide.
[0458] Moreover, in the embodiment shown in FIGS. 21 to 24, the
spotting head 5 is moved in the main scanning direction and the
sub-scanning direction by moving the base plate 164 along the pair
of rails 163, 163 in the sub-scanning direction indicated by the
arrow Y in FIG. 22 by the sub-scanning pulse motor 162 fixed on the
frame 161 and intermittently driving the endless belt 167 at a
predetermined pitch by the main scanning pulse motor 166 provided
on the movable base plate 164, thereby moving the spotting head 5
fixed on the endless belt 167 in the main scanning direction
indicated by the arrow X in FIG. 22. However, the mechanism for
driving the spotting head 5 is not limited to this arrangement but
the spotting head 5 may be moved in the main scanning direction and
the sub-scanning direction using any of various appropriate
mechanisms.
[0459] Further, in the embodiment shown in FIGS. 21 to 24, although
the biochemical analysis unit 151 is held stationary and the
spotting head 5 is moved in the main scanning direction and the
sub-scanning direction with respect to the biochemical analysis
unit 151 placed on the base plate 160, it is possible to hold the
spotting head 5 stationary and move the base plate 160 on which the
biochemical analysis unit 151 is placed in the main scanning
direction and the sub-scanning direction. Moreover, it is also
possible to move the spotting head 5 in the main scanning direction
or the sub-scanning direction and move the base plate 160 on which
the biochemical analysis unit 151 is placed in the sub-scanning
direction or the main scanning direction.
[0460] Furthermore, in the embodiment shown in FIGS. 21 to 24,
since a number of the absorptive regions 155 are regularly formed
in the biochemical analysis unit 151, the spotting head 5 is moved
at constant pitches without using the CCD camera after the
coordinate values of a number of the absorptive regions 155 are
determined using the CCD camera 7 in the coordinate system in which
the reference position of the spotting head 5 is used as the origin
thereof However, for instance, in the case where a number of the
absorptive regions 155 are not regularly formed in the biochemical
analysis unit 151, it is possible to spot specific binding
substances by confirming the position to which specific binding
substances are to be spotted using the CCD camera 7 while the
spotting head 5 is being moved.
[0461] Moreover, in the above described embodiments, the scanner is
provided with the first laser stimulating ray source 21 for
emitting a laser beam having a wavelength of 640 nm, the second
laser stimulating ray source 22 for emitting a laser beam having a
wavelength of 532 nm and the third laser stimulating ray source 23
for emitting a laser beam having a wavelength of 473 nm. However,
it is not absolutely necessary to use a laser stimulating ray
source as a stimulating ray source and a light emitting diode
stimulating ray source may be used as a stimulating ray source
instead of any of the laser stimulating ray sources. Further, a
halogen ramp may be used as any of the stimulating ray source
provided that light components of a wavelength that does not
contribute to stimulation are cut by a spectral filter.
[0462] According to the present invention, it is possible to
provide a biochemical analysis unit which can prevent noise caused
by the scattering of electron beams released from a radioactive
labeling substance from being generated in biochemical analysis
data even in the case of forming spots of specific binding
substances on the surface of a carrier at high density, which can
specifically bind with a substance derived from a living organism
and whose sequence, base length, composition and the like are
known, specifically binding the spot-like specific binding
substances with a substance derived from a living organism labeled
with a radioactive substance to selectively label the spot-like
specific binding substances with a radioactive substance, thereby
obtaining a biochemical analysis unit, superposing the thus
obtained biochemical analysis unit and a stimulable phosphor layer
together, exposing the stimulable phosphor layer to a radioactive
labeling substance, irradiating the stimulable phosphor layer with
a stimulating ray to excite the stimulable phosphor,
photoelectrically detecting the stimulated emission released from
the stimulable phosphor layer to produce biochemical analysis data,
and analyzing the substance derived from a living organism.
[0463] Further, according to the present invention, it is possible
to provide a biochemical analysis unit which can prevent noise
caused by the scattering of chemiluminescent emission and/or
fluorescence released from a labeling substance which generates
chemiluminescent emission when it contacts a chemiluminescent
substrate and/or a fluorescent substance from being generated in
biochemical analysis data even in the case of forming spots of
specific binding substances on the surface of a carrier at high
density, which can specifically bind with a substance derived from
a living organism and whose sequence, base length, composition and
the like are known, specifically binding the spot-like specific
binding substances with a substance derived from a living organism
labeled with, in addition to a radioactive labeling substance or
instead of a radioactive labeling substance, a labeling substance
which generates chemiluminescent emission when it contacts a
chemiluminescent substrate and/or a fluorescent substance to
selectively label the spot-like specific binding substances
therewith, thereby obtaining a biochemical analysis unit,
photoelectrically detecting chemiluminescent emission and/or
fluorescence released from the biochemical analysis unit to produce
biochemical analysis data, and analyzing the substance derived from
a living organism.
[0464] Furthermore, according to the present invention, it is
possible to provide a biochemical analyzing method which can effect
quantitative biochemical analysis with high accuracy by producing
biochemical analysis data based on a biochemical analysis unit
obtained by forming spots of a specific binding substance on the
surface of a carrier at high density, which can specifically bind
with a substance derived from a living organism and whose sequence,
base length, composition and the like are known, specifically
binding the spot-like specific binding substances with a substance
derived from a living organism labeled with a radioactive labeling
substance, a labeling substance which generates chemiluminescent
emission when it contacts a chemiluminescent substrate and/or a
fluorescent substance, thereby selectively labeling the spot-like
specific binding substances therewith.
* * * * *