U.S. patent application number 10/556945 was filed with the patent office on 2007-05-10 for yarn arrangement device and method for yarn arrangement using the device, yarn arrangement tool, method of manufacturing yarn arranged body, and method of manufacturing living body-related substance immobilizing micro array.
This patent application is currently assigned to Mitsubishi Rayon Co., Ltd.. Invention is credited to Toshihiko Fukuda, Yasuo Hiromoto, Toshinori Sumi.
Application Number | 20070101549 10/556945 |
Document ID | / |
Family ID | 33447409 |
Filed Date | 2007-05-10 |
United States Patent
Application |
20070101549 |
Kind Code |
A1 |
Sumi; Toshinori ; et
al. |
May 10, 2007 |
Yarn arrangement device and method for yarn arrangement using the
device, yarn arrangement tool, method of manufacturing yarn
arranged body, and method of manufacturing living body-related
substance immobilizing micro array
Abstract
A fiber array device for arraying fibers three-dimensionally,
includes: a fiber winding device onto which a fiber is wound; and a
fiber supply device that supplies the fiber to the fiber winding
device, wherein the fiber supply device is provided with a movable
guide that supplies fiber to the fiber winding device while
undergoing relative displacement, and wherein the fiber winding
device has a fiber winding bobbin that winds fiber onto its
circumference as it rotates around a shaft, and fiber array flat
plates a plurality of which are stacked respectively at a plurality
of predetermined positions on the circumference of the fiber
winding bobbin and on whose respective external surfaces the fibers
are arrayed. In addition, there is provided a fiber array jig. It
is thereby possible to array fibers three-dimensionally extremely
efficiently at a high density and with a high degree of
accuracy.
Inventors: |
Sumi; Toshinori;
(Iwakuni-shi, JP) ; Fukuda; Toshihiko; (Otake-shi,
JP) ; Hiromoto; Yasuo; (Iwakuni-shi, JP) |
Correspondence
Address: |
OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.
1940 DUKE STREET
ALEXANDRIA
VA
22314
US
|
Assignee: |
Mitsubishi Rayon Co., Ltd.
6-41, Konan 1-chome Minato-ku
Tokyo
JP
108-8506
|
Family ID: |
33447409 |
Appl. No.: |
10/556945 |
Filed: |
May 17, 2004 |
PCT Filed: |
May 17, 2004 |
PCT NO: |
PCT/JP04/06997 |
371 Date: |
November 16, 2005 |
Current U.S.
Class: |
19/144 |
Current CPC
Class: |
C40B 40/06 20130101;
B01J 2219/00722 20130101; B01J 2219/00524 20130101; B01J 2219/00585
20130101; B01J 2219/00673 20130101; B01J 2219/00515 20130101; B65H
54/08 20130101; B65H 55/04 20130101; B01J 19/0046 20130101 |
Class at
Publication: |
019/144 |
International
Class: |
D01G 27/00 20060101
D01G027/00 |
Foreign Application Data
Date |
Code |
Application Number |
May 19, 2003 |
JP |
2003-140728 |
Claims
1. A fiber array device for arraying fibers three-dimensionally,
comprising: a fiber winding device onto which a fiber is wound; and
a fiber supply device that supplies the fiber-to the fiber winding
device, wherein the fiber supply device is provided with a movable
guide that supplies fiber to the fiber winding device while
undergoing relative displacement, and wherein the fiber winding
device has a fiber winding bobbin that winds fiber onto its
circumference as it rotates, and fiber array flat plates a
plurality of which are stacked respectively at a plurality of
predetermined positions on the circumference of the fiber winding
bobbin and on whose respective external surfaces the fibers are
arrayed.
2. The fiber array device according to claim 1, wherein a plurality
of concave rows in which fibers are individually arrayed are formed
substantially parallel with each other in an external surface of
the fiber array flat plates, and the fiber array flat plates are
stacked on the circumference such that the concave rows are
perpendicular to a rotation shaft of the fiber winding bobbin.
3. The fiber array device according to claims 1, wherein an array
pitch of fibers that are arrayed on external surfaces of the fiber
array flat plates making up at least one stacked object from among
each of the stacked objects in the plurality of predetermined
positions is different from an array pitch of fibers that are
arrayed on external surfaces of the fiber array flat plates making
up the other stacked objects.
4. The fiber array device according to claim 1, wherein at least
two positioning through holes are formed in the fiber array flat
plates, and supporting colunms that are inserted through the
positioning through holes are provided on the circumference of the
fiber winding bobbin.
5. A fiber array method for arraying fibers three-dimensionally
using the fiber array device according claim 1, comprising: a first
step in which the individual fiber array flat plates are arranged
in the plurality of predetermined positions; a second step in which
the fiber winding bobbin is rotated a predetermined number of
times, and fiber is supplied while the movable guide is being moved
so that the fibers are gradually arrayed on the arranged fiber
array flat plates; and a third step in which the other fiber array
flat plates are each stacked on top of each fiber array flat plate
on which fibers have been arrayed, wherein the second step and
third step are repeated a plurality of times.
6. A method of manufacturing a fiber array body comprising fixing
the fibers that have been arrayed three-dimensionally using the
fiber array method according to claim 5.
7. The method of manufacturing a fiber array body according to
claim 6, wherein a curable resin is used to fill gaps between the
fibers and is then cured so as to fix the fibers.
8. The method of manufacturing a fiber array body according to
claim 6, wherein organism related substance is fixed in advance to
the fibers.
9. The method of manufacturing a fiber array body according to
claim 6, wherein organism related substance is fixed to fixed
fibers.
10. A method of manufacturing an organism related substance fixed
microarray, comprising slicing the fiber array body manufactured
using the method according to claim 8 into thin pieces in a
direction intersecting the fibers.
11. A fiber wound object comprising: a fiber winding device that
has a fiber winding bobbin and stacked objects made up of two or
more fiber array flat plates that have each been stacked at a
plurality of predetermined positions on the circumference of the
fiber winding bobbin; and fibers that are arrayed and wound onto an
external surface of each fiber array flat plate.
12. The fiber wound object according to claim 11, wherein an array
pitch of fibers that are arrayed on external surfaces of the fiber
array flat plates making up at least one stacked object from among
each of the stacked objects in the plurality of predetermined
positions is different from an array pitch of fibers that are
arrayed on external surfaces of the fiber array flat plates making
up the other stacked objects.
13. A fiber array jig for arraying a plurality of fibers
three-dimensionally, comprising: a plurality of fiber array flat
plates on one surface of each of which a plurality of concave rows
in which fibers are individually arrayed are formed substantially
parallel with each other; and a positioning member that is used to
place these fiber array flat plates in predetermined positions,
wherein at least two of the fiber array flat plates are placed
apart from each other by the positioning member such that the
concave rows formed on these fiber array flat plates are in
alignment with each other, and one or more of the other fiber array
flat plates is stacked on top of these fiber array flat plates.
14. The fiber array jig according to claim 13, wherein at least two
positioning through holes are formed in each of the fiber array
flat plates, and the positioning member is provided with supporting
columns that place each fiber array flat plate in a predetermined
position by being inserted through each of the positioning through
holes.
15. A method for manufacturing a fiber arrayed body comprising: a
fiber array step in which a plurality of fibers are arrayed
three-dimensionally using the fiber arrayjig according to claim 13;
and a fiber fixing step in which the three-dimensionally arrayed
fibers are fixed.
16. The method of manufacturing a fiber array body according to
claim 15, wherein the fiber array step comprises: a first step in
which at least two of the fiber array flat plates are placed apart
from each other by the positioning member such that the concave
rows formed on these fiber array flat plates are in alignment with
each other; a second step in which fibers are individually arrayed
so as to span across the concave rows that are positioned in
alignment with each other; a third step in which other fiber array
flat plates are stacked respectively on top of the at least two
fiber array flat plates; and a fourth step in which tension is
imparted to the arrayed fibers, wherein each of the second step
through fourth step is repeated a plurality of times.
17. The method of manufacturing a fiber array body according to
claim 15, wherein the fiber array step comprises: a first step in
which at least one of the fiber array flat plates is placed in a
predetermined position by the positioning member; a second step in
which a fiber array flat plate that has completed fiber bonding is
manufactured by arraying and bonding one by one ends on one side of
fibers that have been cut to a predetermined length in the concave
rows in the other one of the fiber array flat plates; a third step
in which ends on the other side of the arrayed and bonded fibers
are arrayed one by one in the concave rows of the fiber plate that
was placed in the predetermined position; a fourth step in which
another fiber array flat plate is stacked by the positioning member
on top of the fiber array flat plate that was placed in the
predetermined position; a fifth step in which the fiber array flat
plate that has completed fiber bonding is placed apart by the
positioning member from the fiber array flat plate that was placed
in the predetermined position such that the concave rows formed on
the fiber array flat plate that has completed fiber bonding are in
alignment with the concave rows formed on the fiber array flat
plate that was placed in the predetermined position; and a sixth
step in which tension is imparted to the arrayed fibers, wherein
each of the second step through sixth step is repeated a plurality
of times.
18. The method of manufacturing a fiber array body according to
claim 17, wherein, the second step comprises a step in which the
fiber array flat plates are mounted on drum faces of a fiber
winding drum that rotates around a shaft and are rotated, and fiber
is continuously supplied to the fiber winding drum so that the
fibers are arrayed in sequence in the plurality of concave rows
that are formed in the fiber array flat plates, and thereafter the
arrayed fibers are cut off outside the fiber array flat plates.
19. The method of manufacturing a fiber array body according to
claim 15, wherein, in the fiber fixing step, a curable resin is
used to fill gaps between the three-dimensionally arrayed fibers
and is then cured.
20. The method of manufacturing a fiber array body according to
claim 15, wherein organism related substance is fixed in advance to
the fibers.
21. The method of manufacturing a fiber array body according to
claim 15, wherein, after the fiber fixing step, organism related
substance is fixed to the fibers.
22. A method of manufacturing an organism related substance fixed
microarray, comprising slicing the fiber array body manufactured
using the method according to claim 20 into thin pieces in a
direction intersecting the fibers.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to a fiber array device for
arraying a plurality of fibers three dimensionally, a fiber array
method that uses this device, and a fiber wound object and fiber
array body obtained by arraying fibers using this method. The
present invention also relates to a jig for arraying a plurality of
fibers three-dimensionally and a method of manufacturing a fiber
array body that uses this jig. Furthermore, the present invention
relates to a method of manufacturing from the fiber array body a
microarray to which organism related substance has been fixed that
is used to examine and detect specific organism related
substance.
[0003] 2. Description of Related Art
[0004] An analysis method known as the DNA microarray method (also
known as the DNA chip method) is known as a method of performing
collective expression analysis of multiple genes.
[0005] In this method, using a flat substrate piece that is known
as a microarray or chip (referred to below as a DNA microarray) on
which a number of DNA fragments have been arrayed at a high density
and also fixed in position, the detection and quantification of
nucleic acids based on inter nucleic acid hybridization reactions
is performed on the individual fixed DNA fragments.
[0006] Using this method, the reaction sample only needs to be very
small, and a large variety of reaction specimens can be analyzed
and quantified rapidly and statistically with excellent
repeatability.
[0007] An example of a specific DNA microarray method is a method
in which a sample is taken of the expressed genes of cells or the
like being researched that have been identified using fluorescent
dye or the like, and, by then performing hybridization on this
sample on a DNA microarray, complementary nucleic acids (DNA or
RNA) are bonded together. These bond locations are then read using
a suitable fluorescence detector.
[0008] According to this method, the respective gene quantities in
the sample can be measured quickly.
[0009] An example of technology for fixing an organism related
substance such as nucleic acids on a microarray is a method that,
as is described in Japanese Patent Application Unexamined
Publication No. 2001-239594, uses fiber as a fixed carrier for
organism related substance.
[0010] In this method, firstly, a fiber array body in which a
plurality of fibers, which are fixed carriers, have been arrayed
three-dimensionally in an orderly manner is prepared. This fiber
array body is then sliced into thin pieces. As a result,
microarrays in the form of thin pieces on which fibers are arrayed
two-dimensionally at high density are obtained. In addition, here,
in order to manufacture a fiber array body on which a plurality of
fibers have been arrayed systematically, a plurality of jigs that
have holes in the same pattern as the desired array pattern are
used together.
[0011] Specifically, firstly, these jigs are laid out such that the
positions of the holes are lined up in mutual contact. Fibers,
which are fixed carriers for organism related substance, are then
made to penetrate respectively those holes in the jigs that are in
the same positional relationship. Next, the gap between the jigs is
increased so that tension is imparted to the respective fibers that
are arrayed three-dimensionally between the jigs, and the fibers
are aligned. The gaps between the fibers are then filled using
hardening resin and the fibers are fixed when the resin
hardens.
[0012] The fiber array body that is obtained by fixing the resin in
this manner is then sliced perpendicularly to the longitudinal
direction of the fibers. As a result, an organism related substance
fixed microarray is obtained. Note that, here, it is also possible
to fix organism related substance in the fibers in advance. It is
also possible to align a plurality of fibers and, after these
fibers have been fixed by resin or the like, fix organism related
substance to each fiber.
[0013] According to this method, it is possible to simultaneously
manufacture a large number of organism related substance fixed
microarrays in the same array.
[0014] On the other hand, there is also a need for organism related
substance fixed microarrays that have a large number of fibers per
unit surface area, namely, that have a large number of types of
fixed organism related substance per unit area. In order to
increase the number of fibers, it is necessary to reduce the array
spacing (i.e., the array pitch) between fibers. Furthermore, there
are demands for the outer diameter of the fibers to be made more
narrow and also for the diameter of the holes into which the fibers
are inserted to be made smaller.
[0015] However, in the method described in Japanese Patent
Application Unexamined Publication No. 2001-239594, as is described
above, a plurality of jigs in which a large number of holes have
been formed are used, and it is necessary to insert a single fiber
through each one of the holes. Accordingly, if the array pitch,
hole diameter, and fiber outer diameter are reduced in size, the
following problems occur.
[0016] Namely, in the procedure to guide a fiber that is to be
inserted into a hole to a hole, and in the procedure to insert the
fiber and the like, normally, minute forceps and nozzles are used
to move the fibers. However, at such times, fibers that have
already been inserted in adjacent holes tend to obstruct the
operation of the forceps and nozzles. This tendency is particularly
noticeable when the array pitch, hole diameter, and fiber outer
diameter are made smaller. Moreover, if the outer diameter of the
fibers is reduced in size, there is a deterioration in the fiber
rigidity, and the problem arises that inserting the fibers in the
holes is made even more difficult.
[0017] As is described above, in a conventional process to
manufacture a fiber array body that uses fibers as a carrier for
fixing organism related substance, it is difficult to array the
fibers at a high density with any degree of efficiency and, in
large volume industrial production in particular, this lack of
efficiency is a major problem.
[0018] As a result of repeated thorough investigations in light of
the above described circumstances, the present inventors discovered
that, when manufacturing a fiber array body that uses fibers as
carriers for fixing organism related substance, by using a specific
device and jig for arraying fibers, it is possible to manufacture
fiber arrayed bodies extremely efficiently in which the fibers are
arrayed at a high density and with great precision, and thus
realized the present invention. Accordingly, it is an object of the
present invention to provide a fiber array device and a fiber array
jig that enable fiber arrayed bodies and the like to be
manufactured extremely efficiently, at a high density, and with
great precision.
SUMMARY OF THE INVENTION
[0019] In order to solve the above described problems, the present
invention is a fiber array device for arraying fibers
three-dimensionally, that comprises: a fiber winding device onto
which a fiber is wound; and a fiber supply device that supplies the
fiber to the fiber winding device, wherein the fiber supply device
is provided with a movable guide that supplies fiber to the fiber
winding device while undergoing relative displacement, and wherein
the fiber winding device has a fiber winding bobbin that winds
fiber onto its circumference as it rotates, and fiber array flat
plates a plurality of which are stacked respectively at a plurality
of predetermined positions on the circumference of the fiber
winding bobbin and on whose respective external surfaces the fibers
are arrayed.
[0020] It is preferable that a plurality of concave rows in which
fibers are individually arrayed are formed substantially parallel
with each other in an external surface of the fiber array flat
plates, and that the fiber array flat plates are stacked on the
circumference such that the concave rows are perpendicular to a
rotation shaft of the fiber winding bobbin.
[0021] It is also possible for an array pitch of fibers that are
arrayed on external surfaces of the fiber array flat plates making
up at least one stacked object from among each of the stacked
objects in the plurality of predetermined positions to be different
from an array pitch of fibers that are arrayed on external surfaces
of the fiber array flat plates making up the other stacked
objects.
[0022] It is preferable that at least two positioning through holes
are formed in the fiber array flat plates, and that supporting
columns that are inserted through the positioning through holes are
provided on the circumference of the fiber winding bobbin.
[0023] The fiber array method of the present invention is a method
for arraying fibers three-dimensionally using the above described
fiber array device that comprises: a first step in which the
individual fiber array flat plates are arranged in the plurality of
predetermined positions; a second step in which the fiber winding
bobbin is rotated a predetermined number of times, and fiber is
supplied while the movable guide is being moved so that the fibers
are gradually arrayed on the arranged fiber array flat plates; and
a third step in which the other fiber array flat plates are each
stacked on top of each fiber array flat plate on which fibers have
been arrayed, wherein the second step and third step are repeated a
plurality of times.
[0024] It is preferable that the fibers are at least one selected
from a group consisting of synthetic fibers, semi-synthetic fibers,
regenerated fibers, inorganic fibers, and natural fibers.
[0025] The method of manufacturing a fiber array body of the
present invention is a method in which the fibers that have been
arrayed three-dimensionally using the above described fiber array
method are fixed. At this time, it is preferable that a curable
resin is used to fill gaps between the fibers and is then cured so
as to fix the fibers.
[0026] It is also possible for organism related substance to be
fixed in advance to the fibers, and it is also possible to fix
organism related substance to fixed fibers.
[0027] The method of manufacturing a microarray in which organism
related substance has been fixed of the present invention is a
method in which the fiber array body is sliced into thin pieces in
a direction intersecting the fibers.
[0028] A fiber wound object of the present invention comprises: a
fiber winding device that has a fiber winding bobbin and stacked
objects made up of two or more fiber array flat plates that have
each been stacked at a plurality of predetermined positions on the
circumference of the fiber winding bobbin; and fibers that are
arrayed and wound onto an external surface of each fiber array flat
plate.
[0029] It is also possible for an array pitch of fibers that are
arrayed on external surfaces of the fiber array flat plates making
up at least one stacked object from among each of the stacked
objects in the plurality of predetermined positions to be different
from an array pitch of fibers that are arrayed on external surfaces
of the fiber array flat plates making up the other stacked
objects.
[0030] Furthermore, in order to solve the above described problems,
the present invention is a fiber array jig for arraying a plurality
of fibers three-dimensionally, that comprises: a plurality of fiber
array flat plates on one surface of each of which a plurality of
concave rows in which fibers are individually arrayed are formed
substantially parallel with each other; and a positioning member
that is used to place these fiber array flat plates in
predetermined positions, wherein at least two of the fiber array
flat plates are placed apart from each other by the positioning
member such that the concave rows formed on these fiber array flat
plates are in alignment with each other, and one or more of the
other fiber array flat plates is stacked on top of these fiber
array flat plates.
[0031] It is preferable that at least two positioning through holes
are formed in each of the fiber array flat plates, and that the
positioning member is provided with supporting columns that place
each fiber array flat plate in a predetermined position by being
inserted through each of the positioning through holes.
[0032] The method of manufacturing a fiber arrayed body of the
present invention is a method that comprises: a fiber array step in
which a plurality of fibers are arrayed three-dimensionally using
the above described fiber array jig; and a fiber fixing step in
which the three-dimensionally arrayed fibers are fixed.
[0033] An example of a first mode of the above described fiber
array step is a method that comprises: a first step in which at
least two of the fiber array flat plates are placed apart from each
other by the positioning member such that the concave rows formed
on these fiber array flat plates are in alignment with each other;
a second step in which fibers are individually arrayed so as to
span completely across the concave rows that are positioned in
alignment with each other; a third step in which other fiber array
flat plates are stacked respectively on top of the at least two
fiber array flat plates; and a fourth step in which tension is
imparted to the arrayed fibers, wherein each of the second step
through fourth step is repeated a plurality of times.
[0034] An example of a second mode of the above described fiber
array step is a method that comprises: a first step in which at
least one of the fiber array flat plates is placed in a
predetermined position by the positioning member; a second step in
which a fiber array flat plate that has completed fiber bonding is
manufactured by arraying and bonding one by one ends on one side of
fibers that have been cut to a predetermined length in the concave
rows in the other one of the fiber array flat plates; a third step
in which ends on the other side of the arrayed and bonded fibers
are arrayed one by one in the concave rows of the fiber plate that
was placed in the predetermined position; a fourth step in which
another fiber array flat plate is stacked by the positioning member
on top of the fiber array flat plate that was placed in the
predetermined position; a fifth step in which the fiber array flat
plate that has completed fiber bonding is placed apart by the
positioning member from the fiber array flat plate that was placed
in the predetermined position such that the concave rows formed on
the fiber array flat plate that has completed fiber bonding are in
alignment with the concave rows formed on the fiber array flat
plate that was placed in the predetermined position; and a sixth
step in which tension is imparted to the arrayed fibers, wherein
each of the second step through sixth step is repeated a plurality
of times.
[0035] The second step of the above second mode preferably
comprises a step in which the fiber array flat plates are mounted
on drum faces of a fiber winding drum that rotates around a shaft
and are rotated, and fiber is continuously supplied to the fiber
winding drum so that the fibers are arrayed in sequence in the
plurality of concave rows that are formed in the fiber array flat
plates, and thereafter the arrayed fibers are cut off outside the
fiber array flat plates.
[0036] It is preferable that the fibers are at least one selected
from a group consisting of synthetic fibers, semi-synthetic fibers,
regenerated fibers, inorganic fibers, and natural fibers.
[0037] In the fiber fixing step, it is preferable that a curable
resin is used to fill gaps between the three-dimensionally arrayed
fibers and is then cured.
[0038] Moreover, it is preferable that organism related substance
is fixed in advance to the fibers, or that, after the fiber fixing
step, organism related substance is fixed to the fibers.
[0039] The method of manufacturing a microarray in which organism
related substance has been fixed of the present invention is a
method in which a fiber array body manufactured using the above
described method is sliced into thin pieces in a direction
intersecting the fibers.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] FIG. 1 is a perspective view showing an example of the fiber
array device of the present invention.
[0041] FIG. 2 is an enlarged perspective view of a movable guide
provided in the fiber array device shown in FIG. 1.
[0042] FIG. 3A is a perspective view and FIG. 3B is a frontal view
of a fiber winding bobbin provided in the fiber array device shown
in FIG. 1.
[0043] FIG. 4A is a perspective view of a precise pitch flat plate
and FIG. 4B is a perspective view of an enlarged pitch flat plate
provided in the fiber array device shown in FIG. 1.
[0044] FIG. 5 is a frontal view showing a state in which the fiber
array flat plates shown in FIGS. 4A and 4B are positioned and
stacked in predetermined positions on the circumference of the
fiber winding bobbin shown in FIGS. 3A and 3B.
[0045] FIG. 6 is a frontal view showing an example of a fiber wound
object of the present invention.
[0046] FIG. 7 is a perspective view showing an example of a fiber
array body manufactured using the present invention.
[0047] FIG. 8 is a perspective view showing an example of an
organism related substance fixed microarray manufactured using the
present invention.
[0048] FIG. 9 is a perspective view showing an example of a potting
block used in the present invention.
[0049] FIG. 10 is an explanatory view illustrating a method of
manufacturing a fiber array body of the present invention.
[0050] FIG. 11 is an explanatory view illustrating a method of
manufacturing a fiber array body of the present invention.
[0051] FIG. 12 is a perspective view showing one method of
introducing organism related substance into each fiber of a fiber
array body.
[0052] FIG. 13 is a perspective view showing an example of a fiber
array jig of the present invention.
[0053] FIG. 14A is a perspective view showing a fiber array flat
plate and FIG. 14B is a perspective view showing a positioning
member forming the fiber array jig shown in FIG. 13.
[0054] FIG. 15 is a perspective view showing another example of the
fiber array jig of the present invention.
[0055] FIG. 16 is a perspective view showing an example of a fiber
array body manufactured using the present invention.
[0056] FIG. 17 is a perspective view illustrating a first step of a
first embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0057] FIG. 18 is a perspective view illustrating a second step of
a first embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0058] FIG. 19 is a perspective view illustrating a third step of a
first embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0059] FIG. 20 is a perspective view illustrating a temporary
fixing step of a first embodiment of a fiber arraying process that
uses the fiber array jig shown in FIG. 13.
[0060] FIG. 21 is a perspective view illustrating a fourth step of
a first embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0061] FIG. 22 is a side view showing a state in which fibers are
arrayed three-dimensionally and tension is applied to each fiber
using the fiber array jig shown in FIG. 13.
[0062] FIG. 23 is a perspective view illustrating a first step of a
second embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0063] FIG. 24 is a perspective view illustrating a second step of
a second embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0064] FIG. 25 is a perspective view illustrating a third step of a
second embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0065] FIG. 26 is a perspective view illustrating a fourth step of
a second embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0066] FIG. 27 is a perspective view illustrating a temporary
fixing step of a second embodiment of a fiber arraying process that
uses the fiber array jig shown in FIG. 13.
[0067] FIG. 28 is a perspective view illustrating a fifth step of a
second embodiment of a fiber arraying process that uses the fiber
array jig shown in FIG. 13.
[0068] FIG. 29A is a plan view and FIG. 29B is a side view of a
winding mechanism that can be used in the second step of the
aforementioned second embodiment.
[0069] FIG. 30 is a side view illustrating a fiber fixing step in
the present invention.
[0070] FIG. 31 is a perspective view showing an example of a
potting block used in the fiber fixing step.
[0071] FIG. 32 is a side view illustrating a fiber fixing step in
the present invention.
[0072] FIG. 33 is a side view illustrating a fiber fixing step in
the present invention.
[0073] FIG. 34 is a perspective view showing another example of a
fiber array body of the present invention.
[0074] FIG. 35 is a side view showing yet another example of a
fiber array body of the present invention.
[0075] FIG. 36 is a perspective view showing an example of an
organism related substance fixed microarray manufactured using the
present invention.
[0076] FIG. 37 is a perspective view showing one method of
introducing organism related substance into each fiber of a fiber
array body.
DETAILED DESCRIPTION OF THE INVENTION
[0077] The present invention will now be described in detail.
[Fiber Array Device]
[0078] FIG. 1 is a perspective view showing a state in which fibers
1 are arrayed three-dimensionally using a fiber array device 10 of
the present invention.
[0079] This fiber array device 10 is equipped with a fiber winding
device 11 on which the fibers 1 are wound, and a fiber supply
device 12 that supplies fibers to the fiber winding device 11.
These are mounted on a base 13 so as to form the fiber array device
10.
[0080] The fiber supply device 12 of this example is formed by a
fiber supply bobbin 14 on which the fibers 1 are wound, a guide
roller 15 that sends the fibers 1 forward, and a movable guide 16
(described below in detail). Fibers 1 from the fiber supply bobbin
14 are supplied to the fiber winding device 11 via the guide roller
15 and the movable guide 16.
[0081] Here, as is shown in an enlarged view in FIG. 2, the movable
guide 16 is formed in a nozzle shape into which the fibers 1 are
inserted, and is able to move in both a vertical direction (i.e., a
Z axial direction) and a horizontal direction (i.e., an X axial
direction).
[0082] Specifically, the symbol 17 in FIG. 1 indicates an X axial
stage whose bottom surface is fixed to the top of the base 13 such
that a cross section thereof is formed as a rectangular column and
the longitudinal direction thereof is aligned in a horizontal
direction. An X axial movement table 17a is provided on a top
surface of this stage and moves in a horizontal direction along
this surface. The symbol 18 in FIG. 1 indicates a Z axial stage,
one side surface of which is fixed to the X axial movement table
17a such that, in the same manner, a cross section thereof is
formed as a rectangular column and the longitudinal direction
thereof is aligned in a vertical direction. A Z axial movement
table 18a is provided on a side surface that forms a right angle
with a side surface of this stage and moves in a vertical direction
along this surface. The movable guide 16 is able to move freely in
a vertical direction and horizontal direction in conjunction with
the Z axial movement table 18a as it is fixed to the Z axial
movement table 18a. As a result of this movement, the fibers 1 are
able to be supplied to the fiber winding device 11.
[0083] Note that the horizontal direction in which the movable
guide 16 is able to move is a direction that is parallel with the
shaft 19a of the fiber winding bobbin (described below) indicated
by the symbol 19.
[0084] A control device (not shown) that controls movement of the
movable guide 16 is provided on the movable guide 16. The timings,
directions, and distances of movements by the movable guide 16 can
be optionally controlled by this control device.
[0085] For example, it is possible for an operator to input into
the control device using an operating keyboard 20 instructions as
to how far and in which direction the movable guide 16 is to move
each time the fiber winding bobbin 19 makes one rotation. A motor
40 that is provided with a rotation angle detecting mechanism such
as a rotary encoder is connected to the fiber winding bobbin 19,
and a signal is sent to the control device each time the fiber
winding bobbin 19 rotates. By employing such a structure, the
movable guide 16 moves in accordance with commands from the control
unit in conjunction with the rotation of the fiber winding bobbin
19.
[0086] It is preferable that an inner diameter of the nozzle-shaped
movable guide 16 is formed so as to be 10 to 80% and, more
preferably, 30 to 50% larger than the outer diameter of the fibers
1. It is also preferable that the outer diameter of the
nozzle-shaped movable guide 16 is formed so as to be 40 to 150%
and, more preferably, 70 to 100% larger than the inner diameter
thereof. The length of the nozzle-shaped portion may also be 5 to
30 times the outer diameter and, more preferably, 10 to 20 times
the outer diameter. It is also preferable that the nozzle-shaped
movable guide 16 is formed from stainless steel.
[0087] The fiber winding device 11 provided in the fiber array
device 10 of this example is formed having a fiber winding bobbin
19 that winds the fibers 1 onto its circumference as it rotates
around the shaft 19a, and fiber array flat plates, two or more of
which are stacked at each of a plurality of predetermined positions
on the circumference of the fiber winding bobbin 19, and on whose
outer surface the fibers 1 are arrayed.
[0088] As is shown in FIGS. 3A and 3B, the fiber winding bobbin 19
is formed as a hexagonal column, and is mounted on the base 13 such
that the axial direction thereof is a horizontal direction. The
fiber winding bobbin 19 rotates around the shaft 19a.
[0089] Four supporting columns 21a and 21b are provided on each of
the six side surfaces of the hexagonal columns so as to be
perpendicular to the surfaces. The overall fiber winding bobbin 19
accordingly has a total of 24 supporting columns 21a and 21b. In
particular, these supporting columns 21a and 21b are provided in
groups of two on each side surface in the vicinity of the
boundaries between adjacent side surfaces. The distance between the
two is a short distance (i.e., a pitch D.sub.1) for one group and a
broad distance (i.e., a pitch D.sub.2) for the other group.
Hereinafter, the supporting columns provided at the pitch D.sub.1
will be referred to as the precise pitch supporting columns 21a,
while the supporting columns provided at the pitch D.sub.2 will be
referred to as the broad pitch supporting columns 21b. In this
example, there are six groups each of both the precise pitch
supporting columns 21a and the broad pitch supporting columns
21b.
[0090] The fiber array device 10 of this example is provided with
60 each of the two types of fiber array flat plates 22a and 22b
shown in FIGS. 4A and 4B to make a total of 120.
[0091] Ten concave rows 23a, each having the same shape and in each
of which is arrayed a single fiber 1, are formed substantially in
parallel with each other on one side of the rectangular fiber array
flat plates 22a (referred to below as the precise pitch flat
plates) shown in FIG. 4A. In the same way as in the precise pitch
array plates 22a, the rectangular fiber array flat plates (referred
to below as the broad pitch flat plates) 22b shown in FIG. 4B have
ten concave rows 23b formed on one surface thereof substantially in
parallel with each other. In this example, the distance between the
concave rows (i.e., the pitch), in particular, and the thickness of
the flat plates is greater in the broad pitch flat plates 22b
compared to the precise pitch flat plates 22a.
[0092] Moreover, in this example, the length (i.e., a direction
following the concave rows) is longer and the width is smaller in
the precise pitch flat plates 22a than in the broad pitch flat
plates 22b. Furthermore, when a cross-sectional configuration in
the vertical direction of the concave rows 23a relative to the
lengthwise direction of the concave rows 23a is rectangular, it is
preferable that the width and depth of the concave rows 23a of the
precise pitch flat plates 22a are within a range of 100 to 125% of
the size of the outer diameter of the arrayed fibers. Furthermore,
in order to make it easier to accurately array fibers and from the
viewpoint of work efficiency when inserting fibers in the concave
rows 23a, it is more preferable that the width and depth of the
concave rows 23a is approximately 110% of the size of the outer
diameter of the fibers 1. On the other hand, it is preferable that
the width and depth of the concave rows 23b of the broad pitch flat
plates 22b is within a range of 105 to 150% of the size of the
outer diameter of the fibers 1. It is possible to array the fibers
1 more accurately in the precise pitch flat plates 22a.
[0093] The precise pitch flat plates 22a of this example are
rectangular flat plates having a thickness of 0.42 mm, a width of
10 mm, and a length of 40 mm. Ten concave rows 23a having a width
of 0.3 mm and a depth of 0.3 mm are formed at a pitch of (i.e., at
intervals of) 0.42 mm along the longitudinal direction on one
surface of the rectangular flat plates 22a. Moreover, the broad
pitch flat plates 22b of this example are rectangular flat plates
having a thickness of 4.5 mm, a width of 8 mm, and a length of 170
mm. Ten concave rows 23b having a width of 0.5 mm and a depth of 2
mm are formed at a pitch of 4.5 mm along the longitudinal direction
on one surface of the rectangular flat plates 22b.
[0094] One circular through hole (indicated by the symbols 24a and
24b) that is used for positioning is formed in the vicinity of both
side ends of the fiber array flat plates 22a and 22b. A pitch
D.sub.3 between two positioning through holes 24a in the precise
pitch flat plates 22a is the same as a pitch D.sub.1 between the
precise pitch supporting columns 21a. In addition, a pitch D.sub.4
between two positioning through holes 24b in the broad pitch flat
plates 22b is the same as a pitch D.sub.2 between the broad pitch
supporting columns 21b. Furthermore, the outer diameters of the
respective supporting columns 21a and 21b are formed smaller than
the inner diameters of the respective positioning through holes 24a
and 24b so as to provide clearance between them.
[0095] Accordingly, by fitting the precise pitch supporting columns
21a together with the positioning through holes 24a of the precise
pitch flat plates 22a, and by fitting the broad pitch supporting
columns 21b together with the positioning through holes 24b of the
broad pitch flat plates 22b, as is shown in FIG. 5, the fiber array
flat plates 22a and 22b can each be accurately located at a
plurality of predetermined positions on the circumference of the
fiber winding bobbin 19. Furthermore, other fiber array flat plates
22a and 22b can each be stacked onto the respective fiber array
flat plates 22a and 22b that have already been placed in position.
Fibers 1 are arrayed at a narrow array pitch on a stacked body 25
made up of precise pitch flat plates 22a that have been stacked in
this manner (described below in detail). Fibers 1 are also arrayed
on a stacked body 26, which is formed by stacking broad pitch flat
plates 22b, at a larger array pitch than that of the stacked body
25 formed by stacking the precise pitch flat plates 22a.
[0096] Note that if these fiber array flat plates 22a and 22b are
positioned and stacked on the circumference of the fiber winding
bobbin 19, the surfaces thereof on which the concave rows 23a and
23b are formed become external surfaces.
[0097] Moreover, in this example, ten layers of the 60 precise
pitch flat plates 22a are stacked on each of the six groups of
precise pitch supporting columns 21 a, while ten layers of the 60
broad pitch flat plates 22b are stacked on each of the six groups
of broad pitch supporting columns 21b. In addition, because ten
concave rows 23a and ten concave rows 23b are formed on the
respective fiber array flat plates 22a and 22b, by using the fiber
array device 10 of this example, it is possible to ultimately stack
ten rows multiplied by ten layers of the fibers 1.
[0098] Note that, in FIG. 5, the precise pitch flat plates 23a are
stacked onto the precise pitch supporting columns 21 a after a
spacer 31 having the same shape as the precise pitch flat plates
22a and on which no concave rows 23a are formed has first been
fitted onto the precise pitch supporting columns 21a.
[0099] There is no particular restriction regarding the materials
or manufacturing methods of the fiber array flat plates 22a and 22b
provided that the concave rows 23a and 23b are formed thereon at
accurate sizes. For example, preferably, the precise pitch flat
plates 22a are made by photo etching concave rows on a stainless
steel flat plate as this provides both anti-corrosiveness and
strength. Alternatively, the precise pitch flat plates 22a may
preferably be made by molding a resin such as polymethyl
methacrylate using a precision injection molding method that
employs precise metal dies. For the broad pitch flat plates 22b,
the same materials and manufacturing methods as for the precise
pitch flat plates 22a can be preferably used. However, in addition
to these, it is also possible to use flat plates in which concave
rows 23a and 23b have been formed by machine working stainless
steel or aluminum flat plates.
[0100] The cross-sectional configuration of the concave rows 23a
and 23b that are formed is not limited to a rectangular
configuration such as that shown in the drawings. Bottom portions
of these concave rows may also be formed having a curved surface
shape to follow the external contour of the fibers 1 (i.e., in a U
shape), or in a trapezoidal shape or V shape.
[0101] Moreover, the fiber array device 10 in the example shown in
FIG. 1 is provided with the fiber winding device 11 and the fiber
supply device 12 described above. This fiber array device 10 is
also provided with a tension imparting device 27 that imparts
tension to the fibers 1 supplied to the fiber supply device 12.
[0102] The tension imparting device 27 of this example is provided
with a torque motor 28 that is connected to the fiber supply bobbin
14, and with a tensioner 29 that is located on the downstream side
of the guide roller 15. When the fiber 1 is being supplied while
the movable guide 16 is moving, as is described above, the tension
imparting device 27 is able to impart constant tension within a
fixed range to the fiber 1 such that the fiber 1 is not excessively
tensioned and is not too loose.
[0103] As is described above, according to the fiber array device
10 of this example, it is possible to accurately array the fibers 1
in ten rows multiplied by ten layers. Moreover, the fibers 1 are
arrayed at a small array pitch in the stacked body 25 of the
precise pitch flat plates 22a. Furthermore, the fibers 1 are
arrayed at a larger array pitch in the stacked body 26 of the broad
pitch flat plates 22b than that in the stacked body 25 of the
precise pitch flat plates 22a. Accordingly, by using this fiber
array device 10, as is described below in detail, it is possible to
obtain two fiber array bodies with the fibers arrayed on one end
side at a precise array pitch and arrayed on the other end side at
an array pitch that is larger than this precise array pitch.
[0104] Moreover, in this example, there are ten concave rows 23a
and 23b formed in each of the fiber array flat plates 22a and 22b.
By stacking these fiber array flat plates 22a and 22b in ten
layers, fibers can be arrayed in ten rows multiplied by ten layers.
The number of concave rows 23a and 23b formed in one fiber array
flat plate 22a or 22b as well as the number of stacked layers are
not restricted provided that there is a plurality of each, and can
be set to a desired number. Preferably, the number of concave rows
23a and 23b that are formed in each fiber array flat plate 22a and
22b is in a range of 5 to 100, while the number of stacked layers
of the fiber array flat plates 22a and 22b is also in a range of 5
to 100.
[0105] It is also possible to change the number of fibers 1 that
are arrayed in each layer by varying the number of concave rows 23a
and 23b that are formed in the fiber array flat plates 22a and 22b
of the respective layers.
[0106] In this example, the pitch between positioning through holes
24a in the precise pitch flat plates 22a is taken as D.sub.3, and
the pitch between positioning through holes 24b in the broad pitch
flat plates 22b is taken as D.sub.4, and D.sub.3 is made equal to
D.sub.4. In this case, it is also necessary for the pitches D.sub.1
and D.sub.2 between the corresponding supporting columns 21a and
21b to be made equal.
[0107] Furthermore, in this example, the fiber winding bobbin 19 is
a hexagonal column, however, the fiber winding bobbin 19 is not
restricted to being a hexagonal column provided that it is able to
wind on fiber 1 by rotating around the shaft 19a. For example, the
fiber winding bobbin 19 may be an angular column having between 3
and 5 or also 7 or more side surfaces, or it may not even be an
angular column. However, an angular column having between 4 and 8
side surfaces, in particular, is preferably used as this enables
fiber 1 to be arrayed with the fiber array flat plates 22a and 22b
placed and stacked stably on the circumference of the fiber winding
bobbin 19.
[0108] The fiber array flat plates 22a and 22b that are provided in
the fiber array device 10 of this example are favorably used as
jigs for accurately arraying fibers 1 in predetermined positions.
However, it is not essential for the concave rows 23a and 23b to be
formed therein. For example, it is also possible to employ a
structure in which a sticky layer or adhesive layer is formed on
the surface of these fiber array flat plates that forms the outer
surface thereof when they are stacked on the circumference of the
fiber winding bobbin 19, and for the fibers 1 to be fixed thereto.
Examples of methods of forming a sticky layer or adhesive layer
include coating a sticky agent or adhesive agent onto the surface
that forms the outer surface of the flat plates, and adhering a
commercially available two-sided tape onto the surface that forms
the outer surface of the flat plates. A material that does not
impregnate the fibers 1 is used for the sticky agent, the adhesive
agent, or the two-sided tape. If a material that does impregnate
the fibers 1 is used, there is a possibility that the fibers 1 will
break during the process to array the fibers 1. A water-soluble
vinyl acetate based adhesive agent is preferably used for the
adhesive agent.
[Fiber Array Method and Fiber Array Object]
[0109] Next, a description will be given of a specific method for
arraying the fibers 1 in ten rows multiplied by ten layers using
the fiber array device 10 of the illustrated example.
[0110] Firstly, a first step is performed in which the positioning
through holes 24a and 24b of the broad pitch flat plates 22b and
the precise pitch flat plates 22a are fitted onto all of the broad
pitch supporting columns 21b and precise pitch supporting columns
21a of the fiber winding bobbin 19, so that one of each of these
flat plates is positioned. At this point, six plates each of the
broad pitch flat plates 22b and the precise pitch flat plates 22a
making a total of twelve plates are placed on the circumference of
the fiber winding bobbin 19. Note that, if necessary, a spacer 31
can be placed on the precise pitch supporting columns 21a prior to
the placement thereon of the precise pitch flat plates 22a.
[0111] Next, a second step is performed in which this fiber winding
bobbin 19 is rotated a predetermined number of times, and the
movable guide 16 is moved by the control device so that the fiber 1
is arrayed on the fiber array flat plates 22a and 22b that have
been put in position.
[0112] Namely, firstly, by rotating the fiber winding bobbin 19
once, the fiber 1 supplied from the movable guide 16 is inserted in
sequence in the concave rows 23a and 23b on one end of the
respective fiber array flat plates 22a and 22b that have been put
in position in the first step. Here, because the concave rows 23b
at one end of the broad pitch flat plates 22b and the concave rows
23a and 23b at one end of the precise pitch flat plates 22a are not
on the same circumference, the fiber 1 is supplied while the
movable guide 16 is moved appropriately in the X axial
direction.
[0113] After the fiber winding bobbin 19 has been rotated once in
this manner, in order to insert the fiber 1 onto the adjoining
concave rows 23a and 23b, the movable guide 16 is moved in the X
axial direction and the fiber winding bobbin 19 is immediately
rotated.
[0114] Ten concave rows 23a or 23b are formed in each one of the
fiber array flat plates 22a and 22b of this example. Accordingly,
by rotating the fiber winding bobbin 19 ten times, the fiber 1 can
be arrayed in sequence as far as the concave rows 23a and 23b at
the other end of the fiber array flat plates 22a and 22b.
[0115] Note that, it is preferable that tension of 1 to 20 mN, and
more preferably, of 5 to 10 mN is imparted by the tension imparting
device 27 to the fibers 1 that are arrayed in this manner.
[0116] It is also preferable that the distance between the distal
end of the movable guide 16 and the fiber winding bobbin 19 is as
short as possible, as this enables an accurate array to be
achieved. It is more preferable that the minimum distance (i.e.,
the clearance) between the distal end of the movable guide 16 and
the concave rows 23a and 23b of the fiber array flat plates 22a and
22b where the fibers 1 from the movable guide 16 are arrayed is
within a constant range of 0.1 to 2 mm.
[0117] After the second step has ended in this manner, a third step
is performed in which the other fiber array flat plates 22a and 22b
are stacked one by one on top of the fiber array flat plates 22a
and 22b on which the fibers 1 have already been arrayed.
[0118] Namely, in the same way as in the first step, the
positioning through holes 24a and 24b of the broad pitch flat
plates 22b and the precise pitch flat plates 22a are fitted onto
all of the broad pitch supporting columns 21b and precise pitch
supporting columns 21a of the fiber winding bobbin 19, so that one
each of the fiber array flat plates 22a and 22b is stacked onto
each group of supporting columns 21a and 21b. At this point, a
total of 24 of the fiber array flat plates 22a and 22b are placed
on the circumference of the fiber winding bobbin 19.
[0119] Once the third step has ended in this manner, once again the
second step is performed in which the fiber winding bobbin 19 is
rotated and the movable guide 16 is moved additionally in the Z
axial direction (i.e., upwards). The fibers 1 are then arrayed in
sequence in the concave rows 23a and 23b of the newly positioned
fiber array flat plates 22a and 22b. The third step is then again
performed.
[0120] By repeating the above described second step and third step
a predetermined number of times and ultimately stacking the fiber
array flat plates 22a and 22b ten times on each group of supporting
columns 21a and 21b so that the fibers 1 are arrayed in all of the
concave rows 23a and 23b of the tenth layer of fiber array flat
plates 22a and 22b, it is possible to array fibers in ten rows by
ten layers. After fibers have been arrayed in the fiber array flat
plates 22a and 22b of the tenth layer, fiber array flat plates 22a
and 22b may be further mounted and stacked on the top thereof such
that the fibers 1 do not become disengaged from the concave rows.
Instead of mounting these fiber array flat plates 22a and 22b, it
is also possible to mount holding plates that have an identical
size and shape to the fiber array flat plates 22a and 22B apart
from having no concave rows 23a and 23b formed therein.
[0121] By arraying fibers in ten rows by ten layers in this manner,
a fiber wound object 30 can be obtained. In particular, the fiber
wound object 30 of this example has six stacked objects 25 formed
by the precise pitch flat plates 22a and six stacked objects 26
formed by the broad pitch flat plates 22b. In these, the array
pitches of the fibers 1 that are arrayed in the fiber array flat
plates 22a and 22b. are different. Accordingly, the fibers 1 are
arrayed at two different array pitches in a single fiber wound
object 30.
[Method of Manufacturing A Fiber Array Body]
[0122] Next, a description will be given of a method of
manufacturing two fiber arrayed bodies 32, such as that shown in
FIG. 7, from the fiber wound object 30 shown in FIG. 6 that has
been obtained using the above described method.
[0123] In this fiber array body 32, a portion of the fibers 2,
which have been arrayed in ten rows by ten layers, that is arrayed
on the precise pitch flat plates 22a (i.e., a portion 25'
positioned between stacked objects 25 that are made up of the
precise pitch flat plates 22a) is fixed in a block shape by a
curable resin 33 with its array pattern being maintained. In
contrast, the array pattern of the portion that is arrayed on the
broad pitch flat plates 22b is maintained by the stacked objects 26
that are made up of the broad pitch flat plates 22b. Briefly (a
more detailed explanation is given below), the portion of this
fiber array body 32 that is fixed by the curable resin 33 is sliced
in a direction that intersects the fibers 2, and, preferably, in a
direction that is substantially perpendicular to the fibers 2 so as
to form thin pieces. As a result, an organism related substance
fixed microarray 35 such as that shown in FIG. 8 is obtained. Note
that, in FIG. 7, the symbol 34 indicates a frame member. The
stacked object 26 that is made up of the broad pitch flat plates
22b is fitted into this frame member 24 so that it does not fall
apart.
[0124] One method of manufacturing this type of fiber array body 32
from the fiber wound object 30 shown in FIG. 6 is a method that
uses a potting block to surround the ten rows by ten layers of the
fibers 1 that are suspended between the stacked objects 25 that are
made up of the precise pitch flat plates 22a.
[0125] Preferably, the potting block that is used is formed in a
cylindrical shape by combining together in the manner shown in FIG.
9 four plate-shaped block pieces 36a, 36b, 36c, and 36d that are
made, for example, from a metal such as aluminum. Moreover, when
these four pieces are combined together in a cylinder shape, it is
preferable that mold release processing is performed by fixing a
sheet-shaped material 37 that is formed from highly non-adhesive
Teflon (registered trademark), polyethylene, polypropylene or the
like on the surfaces of these four pieces that will form inner wall
surfaces and on surfaces thereof where the block pieces will be in
contact with each other. If this type of mold release processing is
performed, then after a hollow portion 36e of the potting block 36
is subsequently filled with a curable resin solution which is then
cured, the potting block 36 can be easily separated from the cured
resin. Instead of performing this mold release processing on the
block pieces 36a, 36b, 36c, and 36d, which are made of metal, it is
also possible to form the potting block itself from a highly
non-adhesive resin.
[0126] A semi-conical notch 38 that, in this example, becomes wider
towards one end thereof is preferably formed in one surface of the
inner wall surfaces of the cylindrical potting block 36. As is
described below, this notch 38 then forms a filling aperture when
the hollow portion 36e of the potting block 36 is later filled with
a curable resin solution.
[0127] As is shown in FIG. 10, this potting block 36 is fixed so as
to enclose the fibers 1 between the stacked objects 25 that are
formed by the precise pitch flat plates 22a, and so that the one
end of the potting block 36 where the filling aperture is not
formed is in close contact with one of the stacked objects 25 of
precise pitch flat plates 22a. At this time, a sealing member
formed from silicon rubber or the like that has peelability and
elasticity is interposed so that the curable resin solution that is
supplied later does not leak out from the close contact portion
between the potting block 36 and the stacked object 25.
[0128] After this, the end of the potting block 36 on the side
where the filling aperture is formed (i.e., the aperture end) is
positioned facing upward, and curable resin solution is poured into
the hollow portion 36e of the potting block 36 through the filling
aperture that is formed in the potting block 36. Subsequently, the
potting block 36 is left undisturbed at a predetermined temperature
for a predetermined length of time so that the supplied curable
resin solution is able to harden.
[0129] Note that when filling the hollow portion 36e with the
curable resin solution, it is preferable that the curable resin
solution is stirred and degassed in advance in a vacuum. If it is
degassed, there are no air gaps inside the resin after it has cured
and the resin sufficiently permeates the space between the fibers
1. It is even more preferable if the curable resin solution is
sufficiently degassed and if the above described resin filling task
is conducted under reduced pressure.
[0130] After the curable resin solution with which the interior of
the potting block 36 has been filled has cured, the potting block
36 is disassembled into the four block pieces 36a, 36b, 36c, and
36d. As a result, the fibers that have been arrayed precisely in
ten rows by ten layers are fixed by resin in a block shape.
[0131] Moreover, in the same way as in the method described above,
the fibers 1 between the stacked objects 25 formed by other precise
pitch flat plates 22a in this fiber wound object 30 are also fixed
using the curable resin 33 so that the state shown in FIG. 11 is
obtained.
[0132] Thereafter, the fibers 1 arrayed in ten rows by ten layers
in this fiber arrayed object 30 are appropriately cut open, and all
of the precise pitch flat plates 22a are removed. Furthermore, by
removing all of the broad pitch flat plates 22b other than the two
stacked objects indicated by the symbols 26a in FIG. 11, two fiber
arrayed bodies 32 in the state shown in FIG. 7 can be obtained.
[0133] Note that the type of curable resin 33 that is used here is
preferably a curable resin solution that is in a low viscosity
state at normal temperature and that is able to fill the hollow
portion 36e of the potting block 36 and then cure at room
temperature, and that after curing is able to be sliced easily by a
cutter or the like into thin pieces having a uniform thickness.
Furthermore, the obtained thin pieces should preferably have
sufficient hardness and elasticity that they do not become chipped
or broken. Examples of this type of curable resin 33 include
two-liquid reaction curable resins such as urethane resins.
[Fiber]
[0134] There is no particular restriction as to the type of fiber 1
that is arrayed and then fixed in the manner described above.
Examples thereof include chemical fibers such as synthetic fibers,
semisynthetic fibers, regenerated fibers, and inorganic fibers as
well as natural fibers and composite fibers of these.
[0135] Representative examples of synthetic fibers include: various
types of polyamide based fibers such as nylon 6, nylon 66, and
aromatic polyamides; various types of polyester based fibers such
as polyethylene terephthalate, polybutylene terephthalate,
polylactic acids, and polyglycolic acids; various types of acrylic
based fibers such as polyacrylonitrile; various types of polyolefin
based fibers such as polyethylene and polypropylene; various types
of polyvinyl alcohol based fibers; various types of polyvinylidene
chloride based fibers; various types of polyvinyl chloride based
fibers and polyurethane based fibers; phenol based fibers; fluorine
based fibers such as polyvinylidene fluoride and
polytetrafluoroethylene; polyalkylene paraoxybenzoate based fibers;
fibers that use (meth)acrylic based resins such as polymethyl
methacrylate; and fibers that use polycarbonate based resins.
[0136] Representative examples of semisynthetic fibers include:
various types of fibers that are based on cellulose based
derivatives that use diacetate, triacetate, chitin, or chitosan as
a raw material; and various types of protein based fibers that are
known as promix.
[0137] Representative examples of regenerated fibers include
various types of cellulose based regenerated fibers such as rayon,
cupra, and polynosic that are obtained using a viscose method, a
copper-ammonia method, or an organic solvent method.
[0138] Representative example of inorganic fibers include glass
fibers, and carbon fibers.
[0139] Representative examples of natural fibers include: vegetable
fibers such as cotton, flax, ramie, and jute; animal fibers such as
wool and silk; and mineral fibers such as asbestos.
[0140] These fibers 1 can be used as is appropriate in the
manufacturing of the fiber arrayed bodies 32, however, as is
described above, because tension is imparted to the fibers 1 when
the fibers 1 are being arrayed, of the above described fibers
polycarbonate based fibers, polyester based fibers, nylon based
fibers, and aromatic polyamide fibers and the like that have a high
modulus of elasticity and yield strength are preferably used.
[0141] Any fibers other than natural fibers that are obtained from
a known fiber forming technology such as a melt spinning method, a
wet spinning method, and a dry spinning method, or from a
combination of these technologies can also be used.
[0142] Furthermore, unprocessed fibers may be used without any
modification thereto for the fibers 1, however, if necessary,
fibers into which a reactive functional group has been introduced
may be used, or fibers that have undergone plasma processing or
irradiation processing using .gamma.-rays or electron beams or the
like may be used.
[0143] Moreover, there is no particular restriction as to the form
of the fibers 1, and they may be in monofilament form or in
multifilament form. In addition, the fibers 1 may be formed by spun
yarn obtained by spinning short fibers. The fibers 1 may also be
hollow fibers or fibers having a porous structure. Hollow fibers
can be manufactured using a known method that employs special
nozzles.
[0144] There is no particular restriction as to the outer diameter
of the fibers 1 and fibers 1 having the desired outer diameter can
be used. However, if the outer diameter is too small, breakages
tend to occur and there is a deterioration in the ease of handling.
On the other hand, the smaller the outer diameter of the fibers 1,
the higher the density at which the fibers 1 are able to be
arrayed. Accordingly, the outer diameter of the fibers 1 is set so
as to provide both ease of handling and the desired arrayed
density. Preferably, the outer diameter of the fibers 1 is 500
.mu.m or less, and more preferably 300 to 100 .mu.m. If a
multifilament fiber is used for the fibers 1, then 83 dtex/36
filament or 82 dtex/45 filament or the like can be used without any
modification.
[0145] For example, a monofilament fiber having an outer diameter
of 150 .mu.m is used for the fibers 1 when the organism related
substance fixed microarray 35 is being manufactured from the fiber
array body 32. When this monofilament fiber is arrayed at an array
pitch of 200 .mu.m, the number of fibers 1 that can be arrayed
inside a 1 cm.sup.2 square is 2400. Accordingly, by fixing one type
of organism related substance in one single fiber, it is possible
to fix 2400 types of organism related substance in each square
centimeter. Moreover, if monofilament porous fibers, monofilament
hollow fibers or monofilament porous hollow fibers having an outer
diameter of approximately 200 .mu.m are arrayed at an array pitch
of 200 .mu.m, a fiber array body 32 in which approximately 1000
fibers 1 are arrayed in each square centimeter can be obtained.
Accordingly, by fixing one type of organism related substance in
one single fiber, it is possible to fix 1000 types of organism
related substance in each square centimeter.
[Method of Manufacturing an Organism Related substance Fixed
Microarray]
[0146] Next, a description will be given of a method of
manufacturing the organism related substance fixed microarray 35
from a fiber array body 32 obtained in the manner described
above.
[0147] Here, if fibers 1 are used in which an organism related
substance has previously been fixed, then by slicing this fiber
array body 32 into thin pieces in a direction intersecting the
fibers 1, as is shown in FIG. 8, the fibers 1 in which organism
related substance has been fixed are fixed by the curable resin 33,
and thin slices of the organism related substance fixed microarray
35 can be obtained on both surfaces of which is exposed a
cross-section of the fibers 1. The device used for slicing can be
appropriately selected, and a microtome, laser, or the like can be
used. The direction of the slices should be a direction that
intersects the longitudinal direction of the fibers 1. Preferably,
it should be a direction that is perpendicular to the longitudinal
direction of the fibers 1.
[0148] If the organism related substance fixed in the fibers 1 is,
for example, a nucleic acid, then by providing a specimen for the
obtained organism related substance fixed microarray 100 and
performing hybridization, it is possible to detect a specific
nucleic acid array present in the specimen using the nucleic acid
fixed to the fibers as a probe.
[0149] Note that if a multifilament fiber or spun yarn or the like
is used for the fibers 1, then it is possible to fix organism
related substance in the gaps between the fiber units. Moreover, if
a hollow or porous fiber is used for the fibers 1, then it is
possible to fix organism related substance in the hollow portions
or in the gaps within the fibers 1.
[0150] If, on the other hand, a porous fiber, a hollow fiber, or
porous hollow fiber in which no organism related substance has been
fixed is used for the fibers 1, then organism related substance can
be fixed thereto using the method described below. [0151] (1) A
well plate 39 (see FIG. 12) is prepared having a liquid that
contains organism related substance placed inside each block. One
end portion of each of the fibers 1 on the side thereof where the
array state is maintained by a frame member 34 and by a stacked
body 26 made up of broad pitch flat plates 22b of the fiber array
body 32 shown in FIG. 7 is inserted into each block. [0152] (2)
Next, by placing the other end of the fibers 1 in a reduced
pressure state so as to suction the liquid, the liquid that
contained the organism related substance is suctioned up into the
hollow portions and porous portions of each of the fibers 1, and
the organism related substance is introduced inside each of the
fibers.
[0153] A commercially available well plate can be used for the well
plate 39. At this time, if the array pitch of the fibers 1 in the
broad pitch flat plates 22b has previously been made the same as
the pitch of each block in the well plate 39, then it is possible
to insert the end portion of each single fiber easily into each
block.
[0154] Note that the type of organism related substance that is
introduced into each fiber 1 may be different in every single one
of the ten rows by ten layers of fibers 1. It is also possible to
group together a plurality of fibers and introduce the same type of
organism related substance into that group. If the types of
organism related substance are all different from each other, it is
possible to obtain an organism related substance fixed chip 35 in
which 100 types of organism related substance has been fixed.
[0155] Examples of the organism related substance that is
introduced into the fibers 1 in this manner include nucleic acids
such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA),
peptide nucleic acid (PNA), and oxypeptide nucleic acid (OPNA) as
well as proteins and polysaccharides.
[0156] If a nucleic acid is used as the organism related substance,
the DNA or RNA from living cells may be prepared using a known
method. For example, DNA may be extracted using Blin's method (see
Blin et. Al., Nucleic Acids Res. 3: 2303 (1976)). RNA may be
extracted using Favaloro's method (see Favaloro et. Al., Methods
Enzymol. 65: 718 (1980)).
[0157] It is also possible to use chain or toroidal plasmid DNA or
chromosome DNA, DNA pieces obtained by slicing these using
restriction enzymes or by chemically slicing them, DNA that has
been synthesized by enzymes in a test tube, or else chemically
synthesized DNA. For example, DNA may be extracted using Blin's
method (see Blin et. Al., Nucleic Acids Res. 3: 2303 (1976)). RNA
may be extracted using Favaloro's method (see Favaloro et. Al.,
Methods Enzymol. 65: 718 (1980)).
[0158] These various organism related substance types may be used
unmodified as they are, or they may be used in the form of
derivatives in which the organism related substance has undergone
chemical modification, or, if necessary, they may transformed and
then used. For example, if a nucleic acid is used for the organism
related substance, then amino formation, biotin formation,
digoxigenin formation and the like, which are known as methods for
chemically modifying organism related substance (Current Protocols
in Molecular Biology, Ed.; Frederick M. Ausubel et. al. (1990) and
Deisotoping Experimental Protocols (1) DIG Hybridization
(shuujunsha)), can be employed.
[0159] As the solution that contains these types of organism
related substance, for example, an acrylamide aqueous solution that
contains organism related substance into which an unsaturated
functional group has been introduced is used. After this solution
has been suctioned into the hollow portion or porous portion or the
like of the fibers, as is described above, it is heated to 50 to
60.degree. C. As a result, a gel in which the organism related
substance has been fixed to the gel network can be fixed to the
hollow portion or porous portion.
[0160] As is described above, when fibers 1 are being arrayed
three-dimensionally, the fiber array device 10 that is used is
equipped with a fiber winding device 11 on which fiber is wound and
a fiber supply device 12 that supplies the fibers 1 to the fiber
winding device 11. The fiber supply device 12 is provided with a
movable guide 16 that supplies fiber while moving relatively to the
fiber winding device 11. The fiber winding device 11 has a fiber
winding bobbin 19 that rotates around a shaft 19a while the fibers
1 are wound onto the circumference thereof, and fiber array flat
plates 22a and 22b, a plurality of which are stacked respectively
at a plurality of predetermined positions on the circumference of
the fiber winding bulb in 19, and on whose respective external
surfaces the fibers 1 are arrayed. As a result, the fibers 1 can be
arrayed at a high density, with a high degree of accuracy, in a
short time, and extremely efficiently, and it also becomes possible
to mass produce the fiber array bodies 32 for industry. Namely, if
this type of fiber array device 10 is used, it is not necessary to
perform the complex task of inserting individual fibers through
holes formed in a jig, as is the case conventionally. Moreover,
because it is not necessary to guide the fibers being inserted into
the holes using forceps or the like, the problem of fibers that
have already being inserted into adjacent holes obstructing the
operation when inserting fibers using forceps does not arise. In
addition, because the operation is not one of inserting the fibers
1 into holes, but of arraying them in the concave rows 21, even if
the outer diameter of the fibers is narrow and they have low
rigidity, they can be arrayed easily so that a greater degree of
density in the array of the fibers 1 becomes possible.
[0161] Namely, by using the fiber array device 10 that is described
above, even if the outer diameter of the fibers 1 is small and they
are difficult to handle, they can still be arrayed accurately at a
high density and also efficiently in a short time, and mass
production of the fiber arrayed bodies 32 becomes possible. As a
result, it is also possible to mass produce organism related
substance fixed microarrays 35 that enable a large variety of
samples to be analyzed.
[0162] Moreover, in particular, the fiber array flat plates 22a and
22b have a plurality of concave rows 23a and 23b, in each one of
which is arrayed a single fiber 1, formed substantially parallel to
each other in an external surface thereof, and the fiber array flat
plates 22a and 22b are stacked on the circumference of the fiber
winding bobbin 19 so that the concave rows 23a and 23b are
perpendicular to the shaft 19a of the fiber winding bobbin 19. As
result, the fibers 1 can be arrayed more accurately and
reliably.
[0163] Furthermore, by using the precise pitch flat plates 22a and
the broad pitch flat plates 22b as the fiber array flat plates 22a
and 22b, it is possible to easily obtain a fiber array body 32 at
one end of which the fibers are arrayed at a precise array pitch,
and at the other end of which the fibers are arrayed at an array
pitch that is broader than this precise array pitch. If this type
of fiber array body 32 is used, then, as is described above, it is
also possible to easily introduce organism related substance to
each fiber 1 using the well plate 39.
EXAMPLES
[0164] The present invention will now be described specifically
using examples.
Example 1
[0165] A fiber array device 10 having the same structure as that
shown in FIG. 1 was used apart from the fact that the broad pitch
flat plates 22b shown in FIG. 4B were completely omitted and 120 of
only the precise pitch flat plates 22a shown in FIG. 4A were
provided, and apart from the fact that twelve groups (i.e., 24
altogether) of only the precise pitch supporting columns 21a were
erected as fiber winding bobbins. Using this fiber array device 10,
a fiber wound object in which polycarbonate hollow fibers having a
diameter of 0.3 mm were arrayed in ten rows by ten layers was
obtained.
[0166] Note that the movement speed in the X axial direction of the
nozzle-shaped movable guide 16 was set at 12000 mm/minute, and the
movement pitch was set at 0.42 mm, which was the same as the pitch
between the concave rows 23a in the precise pitch flat plates 22a.
5 mN of tension was imparted by a tension imparting device to the
hollow fibers that were arrayed in this manner. In addition, the
minimum distance (i.e., the clearance) between the distal end of
the movable guide 16 and the concave rows of the precise pitch flat
plates 22a where the fibers 1 from the movable guide 16 were
arrayed was set at a constant 0.5 mm. The revolution speed of the
fiber winding bobbin 19 was set at 10 rpm. The inner diameter,
outer diameter, and length of the nozzle-shaped movable guide 16
were set respectively at 0.4 mm, 0.7 mm, and 12 mm.
[0167] As a result, in approximately one hour of working time, a
fiber wound object in which fibers 1 were accurately arrayed in ten
rows by ten layers was obtained.
Example 2
[0168] Using the fiber array device 10 shown in FIG. 1, a fiber
wound object 30 such as that shown in FIG. 6 in which polycarbonate
hollow fibers having a diameter of 0.3 mm were arrayed in ten rows
by ten layers was obtained.
[0169] Note that the movement speed in the X axial direction of the
nozzle-shaped movable guide 16 was set at 12000 mm/minute. The
movement pitch was set at 0.42 mm for the precise pitch flat plates
22a, which was the same as the pitch between the concave rows 23a
in the precise pitch flat plates 22a, and was set at 4.5 mm for the
broad pitch flat plates 22b, which was the same as the pitch
between the concave rows 23b in the precise pitch flat plates 22b.
5 mN of tension was imparted by a tension imparting device to the
hollow fibers that were arrayed in this manner. In addition, the
minimum distance (i.e., the clearance) between the distal end of
the movable guide 16 and the concave rows 23a and 23b of the fiber
array flat plates 22a and 22b where the fibers from the movable
guide 16 were arrayed was set at a constant 0.5 mm. The revolution
speed of the fiber winding bobbin 19 was set at 10 rpm.
[0170] As a result, in approximately one hour of working time, a
fiber wound object 30 in which the fibers 1 were arrayed in ten
rows by ten layers at two different array pitches in the same fiber
arrayed object 30 was obtained.
Example 3
[0171] A potting block 36 such as that shown in FIG. 9 was placed
in two locations on portions sandwiched between two stacked objects
25 of the precise pitch flat plates 22a in the fiber wound object
30 obtained in Example 2. As is shown in FIG. 10, a polyurethane
elastomer (coronate 4403/nippolan 4276 mixed in a proportion of
coronate 6: nippolan 4) solution was then poured into the interior
of the hollow portion and hardened so that the state shown in FIG.
11 is obtained. Thereafter, the fibers 1 were cut open and the
fiber array flat plates 22a and 22b were appropriately removed. As
a result, two block-shaped fiber arrayed bodies 32 in which the
fibers 1 were accurately arrayed in the manner shown in FIG. 7 were
prepared from a single fiber wound object 30. The required working
time was approximately one hour up until the pouring of the resin
solution.
Example 4
[0172] A fiber wound object 30 such as that shown in FIG. 6 was
obtained in which the fibers 1 were arrayed in the same manner as
in Example 1 except for the fact that the torque motor 28 of the
tension imparting device 27 was not operated and for the fact that
the above described clearance was 3 mm.
Example 5
[0173] A fiber wound object 30 such as that shown in FIG. 6 was
obtained in which the fibers 1 were arrayed in the same manner as
in Example 1 except for the fact that the fibers 1 were supplied
without being passed through the tensioner 29 of the tension
imparting device 27.
Example 6
[0174] A fiber wound object 30 such as that shown in FIG. 6 was
obtained in which the fibers 1 were arrayed in the same manner as
in Example 1 except for the fact that the clearance was set to 10
mm.
Example 7
[0175] A fiber wound object 30 such as that shown in FIG. 6 was
obtained in which the fibers 1 were arrayed in the same manner as
in Example 1 except for the fact that, instead of concave rows, an
adhesive layer made up of a vinyl acetate based adhesive agent was
formed on the precise pitch flat plates. Thereafter, resin fixing
was performed on the fibers 1 in the same way as in the above
described Example 3 so that two block-shaped hollow fiber arrayed
resin bodies were prepared.
[0176] According to each of the above described examples, it is
possible to array fibers accurately in a short length of time. In
particular, according to Examples 1 to 3, a particularly accurate
fiber array is possible. Moreover, in Example 3, an excellent fiber
array body was obtained in which the fibers remained fixed in this
state.
[0177] In contrast, in Examples 4 and 6, the array state of the
fibers was somewhat inferior compared to that of Examples 1 to 3.
In Example 5, there was a tendency for considerable stress to be
placed on the fibers when the movable guide 16 was being moved.
Comparative Example 1
[0178] For the fiber array jig two stainless steel porous plates
having a thickness of 0.1 mm were used in which a total of 49 holes
having a diameter of 0.32 mm were prepared at a pitch of 0.42 mm
using a photoetching method in seven rows horizontally and seven
rows vertically. 49 lengths of polycarbonate hollow thread (having
an outer diameter of 0.3 mm.times.a length of 1 m) were inserted
into all of the holes in the porous plates, and a gap of 50 mm was
set between the two porous plates.
[0179] Next, the hollow threads between the two porous plates that
were arrayed in this manner were placed inside a potting jig. The
same polyurethane elastomer (i.e., coronate 4403/nippolan 4276) as
that used in Example 3 was then poured into the space enclosed by
the porous plates and the potting jig. As a result, a hollow thread
arrayed body was formed in a block shape whose vertical,
horizontal, and height dimensions were 20 mm.times.20 mm.times.50
mm respectively. The working time was approximately six hours up
until the pouring of the resin solution.
[0180] Next, a detailed description will be given of the fiber
array jig of the present invention and of a method of manufacturing
a fiber array body using this jig.
[Fiber Array Jig]
[0181] The fiber array jig of the present invention is used in
order to array a plurality of fibers three-dimensionally, and a
fiber array body is obtained by fixing the three-dimensionally
arrayed fibers in this state.
[0182] FIG. 13 is a perspective view showing an example of a fiber
array jig 110.
[0183] As is also shown in FIGS. 14A and 14 B, this fiber array jig
110 has ten fiber array flat plates 120 that are made up of
rectangular flat plates, and six concave rows 121, in each one of
which is arrayed a single fiber, are formed substantially parallel
with each other in one surface of these fiber array flat plates
120. The fiber array jig 110 also has a positioning jig 130 for
accurately positioning the fiber array flat plates 120 in
predetermined positions.
[0184] As is shown in FIG. 14A, one circular positioning through
hole (indicated by the symbols 122) is formed in the vicinity of
both ends of each of the fiber array flat plates 120 of this
example. In contrast, as is shown in FIG. 14B, the positioning
member 130 is formed by a base 133 in the form of a rectangular
flat plate, and two groups (with two columns in each group) of
supporting columns 132 (to make a total of four) that stand
vertically relative to the base 133. A spacing D.sub.5 between the
two positioning through holes 122 that are formed in each of the
fiber array flat plates 120 is formed so as to be the same as a
spacing D.sub.6 between each group of the supporting columns 132
that are erected on the base 133. In addition, the outer diameter
of the supporting columns 132 is formed slightly smaller than the
inner diameter of the positioning through holes 122 so that a
sufficient clearance is provided. As is shown in FIG. 13, by
inserting the supporting columns 132 into the positioning through
holes in the respective fiber array flat plates 120, each of the
fiber array flat plates 120 can be accurately placed in a
predetermined position.
[0185] Namely, in the fiber array jig 110 of this example, as is
shown in FIG. 13, using the positioning member 130, two fiber array
flat plates 120 can be placed on the base 133 such that the concave
rows 121 that are formed in the fiber array flat plates 120 are
placed in alignment with each other, and such that a predetermined
spacing W is provided between them. Furthermore, by stacking other
fiber array flat plates 120 on top of the fiber array flat plates
120 that are already placed on the base 133, ultimately, two groups
can be stacked having five layers of the fiber array flat plates
120 in each group.
[0186] Accordingly, by arraying one fiber in each of the concave
rows 121 of each fiber array flat plate 120 (described below in
detail), according to this fiber array jig 110, fibers can be
arrayed in five layers with each layer having six rows.
[0187] Note that the symbol 131 in the drawings indicates a spacer
that is formed by a rectangular plate the same shape as the fiber
array flat plates 120. Two circular positioning through holes are
formed in the vicinity of both ends thereof. The spacers 131 are
positioned using the positioning members 130 by the same method as
that employed for the fiber array flat plates 120. The spacers 131
can be used if necessary, and spacers 131 having the desired
thickness can be used as is appropriate in accordance with the
thickness of the potting block that is used in the fiber fixing
process (described below in detail).
[0188] Here, the width and depth of the concave rows 121 formed in
the fiber array flat plates 120 can be appropriately set in
accordance with the outer diameter of the fibers that are arrayed
in the concave rows 121. When the cross-sectional configuration in
the vertical direction of the concave rows 121 relative to the
lengthwise direction is rectangular, as is the case in this
example, it is preferable that the width and depth are within a
range of 100 to 125% of the size of the outer diameter of the
arrayed fibers. If the width and depth are this size, then the
fibers can be arrayed without protruding from the concave rows 121.
Furthermore, in order to make it easier to accurately array fibers
and from the viewpoint of work efficiency when inserting fibers in
the concave rows 121, it is most preferable that the width and
depth of the concave rows 121 is approximately 110% of the size of
the outer diameter of the fibers. If the concave rows 121 have
uniform dimensions and are deep enough for the fibers not to
protrude and for the fibers to be easily inserted therein, then the
cross-sectional configuration thereof is not limited to the
rectangular configuration shown in the examples in the drawings.
Bottom portions of the concave rows 121 may also be formed having a
curved surface shape to follow the external contour of the fibers
(i.e., in a U shape), or in a trapezoidal shape or V shape.
[0189] The material used to form the fiber array flat plates 120 is
not particularly limited, however, a metal is preferable. In
particular, a stainless steel based spring steel is preferably used
as the metal from the viewpoint of its anti-corrosion properties
and its strength.
[0190] The method used to manufacture the fiber array flat plates
120 only needs to involve preparing a flat, metal plate and then
forming concave rows in one surface thereof. Methods that may be
used to form the concave rows in the flat, metal plate include: 1)
a method in which the concave rows 121 are formed one at a time by
machining; 2) a method in which a plurality of concave rows 121 are
carved out and formed simultaneously using a special edged tool; 3)
and a method in which the concave rows 121 are formed by etching.
In addition to these, 4) another method may be used in which flat,
metal plates (a) having the same thickness as the depth of the
concave rows 121 being formed are prepared, and are then processed
in a lattice configuration by etching. The bar portions forming the
lattice of the lattice-shaped member that is obtained only are then
bonded to another flat, metal plate (b), and by then cutting the
bar portions protruding from the flat, metal plate (b), concave
rows 121 having the same depth as the thickness of the flat, metal
plates (a) being used are formed.
[0191] Among these methods, on methods 1) and 2), because the
concave rows 121 are formed by machining, when forming particularly
detailed concave rows 121, care must be taken that there are no
dimensional changes caused by heat from the machining and no
bending caused by residual stress from the machining, and also that
there are no changes in the width or depth of the concave rows 121
caused by wearing of the cutting edge. In addition, although in the
method based on etching there are no problems with dimensional
changes or bending such as those that may be recognized in methods
1) and 2), it is still necessary to control the depth of the
concave rows 121 by the etching conditions. As a result, it is
necessary for the etching conditions to be suitably set or
regulated. Accordingly, method 4) is preferable as the method for
forming the concave rows 121 because precise concave rows 121 can
be formed without the etching conditions needing to be set and
regulated as strictly as in method 3).
[0192] In this method 4), the method used to bond the lattice
member to the flat, metal plate (b) may be a bonding method using
an adhesive agent, or may be a method in which a thin film of a
metal that will become a binder is formed on a bonding surface of
the lattice member or flat, metal plate (b), and the two are then
bonded together by applying heat and pressure. However, if an
adhesive agent or binder is used, there is a possibility of
unevenness being generated in the thickness of the concave rows 121
due to unevenness in the thickness of the binder or adhesive agent.
There is also a possibility of the concave grooves being narrowed
due to excess binder or adhesive agent spreading from the bonding
surface into the concave rows 121, and a possibility of bending
occurring that is caused by a bimetal effect generated by any
difference in the coefficients of thermal expansion of the
materials. Accordingly, in order to obviate these possibilities, it
is preferable that the same material is used to form the lattice
member and the flat, metal plate (b), and that these are bonded
together using solid phase diffusion bonding in which the metal
structures are integrated and bonded together by applying heat and
pressure to the lattice member and the flat, metal plate (b) in a
vacuum.
[0193] Note that, as is described above, a metal such as a
stainless steel based spring steel is preferably used as the
material of the fiber array flat plates 120, however, provided that
sufficient strength and dimensional accuracy are ensured, it is
also possible to use a thermoplastic synthetic resin, a
thermosetting synthetic resin, a photocurable synthetic resin or
the like. In this case, a method may be used in which these resins
are molded by press molding or injection molding using a precise
metal mold so as to form the fiber array flat plates 120. According
to this type of molding method, identical fiber array flat plates
120 can be manufactured in large quantity and at low cost.
[0194] There is also no particular restriction as to the material
of the positioning member 130, however, it is preferable that
stainless steel or the like that has excellent strength and rust
resistance is used.
[0195] Note that, in the fiber array jig 110 shown in FIG. 13, as
is described above, by fitting the supporting columns 132 of the
positioning member 130 together with the positioning through holes
122 of the respective fiber array flat plates 120, the placement
positions of the plurality of fiber array flat plates 120 can be
decided specifically and accurately. According to this type of
positioning mechanism, positioning can be achieved with a high
degree of accuracy using a simple structure. However, there are no
restrictions on the positioning mechanism provided that the fiber
array flat plates 120 can be positioned specifically and
accurately. For example, as is shown in FIG. 15, a positioning
member that has guide members 135 having a -shaped horizontal cross
section standing on the flat, rectangular plate-shaped base 133
instead of supporting columns can be used as the positioning member
130. In the positioning member 130 shown in FIG. 15, two groups are
provided with each group formed by two -shaped guide members 135
positioned facing each other. The fiber array flat plates 120 are
placed or stacked between the guide members 135 of each group. As a
result, the placement positions of a plurality of fiber array flat
plates 120 can be decided specifically and accurately.
[0196] Moreover, in the fiber array jig 110 shown in FIGS. 13 to
14B, six of the concave rows 121 are formed in each fiber array
flat plate 120, and these fiber array flat plates 120 are stacked
in five layers. As a result, it is possible to array a total of 30
fibers. The number of concave rows 121 that are formed in each
single fiber array flat plate 120 as well as the number of layers
of stacked fiber array flat plates 120 is not restricted provided
that there are a plurality of each, and can be set to desired
numbers. Preferably, the number of concave rows 121 formed in each
fiber array flat plate 120 is in a range of 6 to 100, and more
preferably in a range of 10 to 100. The number of layers of stacked
fiber array flat plates 120 is preferably in a range of 5 to 100,
and more preferably in a range of 10 to 100.
[0197] Moreover, it is also possible to change the number of fibers
that are arrayed in each layer by varying the number of concave
rows 121 that are formed in each fiber array flat plate 120 of the
respective layers.
[0198] Furthermore, there is no particular restriction as to the
spacing W between two fiber array flat plates 120 that are placed
such that the concave rows 121 that are formed in each fiber array
flat plate 120 are placed in alignment with each other, and this
spacing W can be set as is appropriate. Here, if the spacing W is
set as a large spacing, then an elongated product can be obtained
as the fiber array body that is ultimately obtained. If an
elongated product is obtained, then when the fiber array body is
sliced into thin pieces in a direction intersecting the fibers and
an organism related substance fixed microarray is being
manufactured, a large number of organism related substance fixed
microarrays can be obtained from a single fiber array body, which
is advantageous as regards manufacturing costs. However, the larger
the spacing W, the more difficult it becomes to strictly control
the array state of the fibers between the two fiber array flat
plates 120. Accordingly, it is preferable that the spacing W is
suitably set in consideration of these viewpoints.
[0199] Furthermore, in the fiber array jig 110 of this example,
firstly, two fiber array flat plates 120 are positioned and then
the other fiber array flat plates 120 are each stacked on top of
these two plates. As a result, two groups of stacked fiber array
flat plates 120 are formed. It is also possible for three or more
fiber array flat plates 120 to be placed in position and for each
of the other fiber array flat plates 120 to be stacked on top of
these so that three or more groups of stacked fiber array flat
plates 120 are formed provided that the fiber array flat plates 120
are positioned with a predetermined spacing between each such that
the concave rows 121 that are formed in each fiber array flat plate
120 are in alignment with each other. For example, if N number of
groups of stacked fiber array flat plate 120 are being formed, the
fiber array objects can be manufactured as N-1 groups, and it is
necessary for the two supporting columns 132 for each group that
are provided on the positioning member 130 to be two supporting
columns 132 for N groups.
[Method of Manufacturing a Fiber Array Body]
[0200] Next, a description will be given of a method of
manufacturing a fiber array body 150 (see FIG. 16) in which 30
fibers are fixed while being arrayed three-dimensionally. This
fiber array body 150 is obtained by performing a fiber array step
in which 30 fibers are arrayed three-dimensionally using the fiber
array jig 110 shown in FIG. 13, and by then performing a fiber
fixing step in which these fibers are fixed while being in a
three-dimensionally arrayed state. In the fiber array body 150
shown in FIG. 16, 30 fibers 140 are inserted substantially in
parallel with each other in the direction shown by the arrows.
[0201] The symbol 151 indicates a curable resin, and the 30 fibers
are fixed with the spacing between each maintained by this
resin.
(Fiber Array Step)
[0202] Two specific embodiments can be preferably illustrated for
the fiber array step. Firstly, a first embodiment will be
described.
[0203] In the first embodiment, firstly, as is shown in FIG. 17,
the positioning through holes of the respective spacers 131 are
fitted onto the two groups of supporting columns 132 of the
positioning member 130 shown in FIG. 14B, and the two spacers 131
are put in position. Next, two fiber array flat plates 120 are
prepared, and the positioning through holes 122 in each are fitted
respectively onto the two groups of supporting columns 132 of the
positioning members 130. The two fiber array plates 120 are thus
positioned with a predetermined spacing between them such that the
respective concave rows 121 that are formed in the two fiber array
flat plates 120 are in alignment with each other. The above process
makes up a first step.
[0204] Next, as is shown in FIG. 18, a second step is performed in
which six fibers 140 are arrayed individually so as to span the
aligned concave rows 121, namely, such that the fibers 140 do not
cross each other or overlap each other.
[0205] Thereafter, a third step is performed in which, as is shown
in FIG. 19, other fiber array flat plates 120 are stacked
respectively on top of the two fiber array flat plates 120 that
have been positioned by the positioning member 130 and in whose
concave rows 121 individual fibers 140 have been arrayed.
[0206] It is also possible to follow this third step with a fourth
step in which tension is imparted to each of the arrayed fibers
140, however, prior to this, as is shown in FIG. 20, it is
preferable that a temporary fixing step is performed in which, by
further stacking weight members 134 thereon, the tight contact
between the first layer (i.e., the bottom most layer) of fiber
array flat plates 120 and the second layer of fiber array flat
plates 120 on top of the first layer is maintained.
[0207] If this type of temporary fixing is performed, the six
arrayed fibers 140 do not spring out of the concave rows 121, so
that the subsequently performed fourth step can be performed stably
and the work efficiency is improved.
[0208] Namely, the weight members 134, which are heavy objects, are
each placed on the stacked fiber array flat plates 120. At this
time, it is preferable that flat objects such as those shown in the
drawings that have positioning through holes formed in the vicinity
of both ends thereof and are able to be positioned using the
supporting columns 132 are used for the weight members 134, as this
prevents the weight members 134 from being mispositioned or falling
off.
[0209] The fourth step is a step in which tension is imparted to
each of the arrayed fibers 140, and is intended to prevent the
fibers 140 from being fixed in a sagging state in the fiber fixing
step that is performed after the fiber array step. Note that the
size of the tension that is imparted here is within a range whereby
the fibers 140 are not elastically deformed or broken.
[0210] An example of a method used to impart and maintain the
tension to the fibers 140 is a method that uses a tension imparting
device 160 such as that shown in FIG. 21.
[0211] This tension imparting device 160 is provided with a
placement base 161 on which the positioning members 130 are placed
and fixed, a fiber fixing section 162 that fixes one end 140a of
the arrayed fibers 140, and a fixing jig 163 that fixes while
pulling the other end 140b of the fibers 140. The fixing jig 163 is
provided with a holding member 163a such as a clamp that holds the
other end 140b of the fibers 140, and an elastic body 163b such as
a spring or a rubber member that is connected to the holding member
163a. The elastic body 163b can be fixed to a flat plate 164 on
which the placement base 161 is mounted, and this enables the
fibers 140 to be maintained in a tensioned state. Note that, in
FIG. 21, the symbol 165 indicates a guide member in the form of a
round bar. This guide member 165 enables the direction in which the
fibers 140 are pulled by the fixing jig 163 to be changed in a 90
degree downward direction, as is shown in FIG. 21. Accordingly, as
is also shown in FIG. 22, even if four layers of fibers 140 are
later arrayed and tension is imparted to each of the fibers 140, it
is still easy to secure a compact space on the base 164 for fixing
the elastic bodies 163b.
[0212] Furthermore, here, it is preferable that the heights of the
tops of the guide members 165 are slightly lower than the heights
of the bottom portions of the concave rows 121 formed in the fiber
array flat plates 120, so that not only is tension imparted in the
longitudinal direction of the fibers 140 to each of the arrayed
fibers 140, but so that force is also acting in a direction in
which the fibers 140 are pressed downwards onto the bottom portions
of the concave rows 121. By employing a structure such as this,
tension is imparted to each fiber 140 to prevent each fiber from
coming loose, and the fibers 140 can be prevented from springing
out of the concave rows 121 even if the topmost layer of fiber
array flat plates 120 or the weight members 134 are removed.
[0213] The fourth step is performed in this manner, so that the
state shown in FIG. 21 is obtained. As a result, the tasks of
arraying the fibers 140 of the first layer in predetermined
positions and imparting tension thereto are ended.
[0214] If the temporary fixing step using the weight members 134 is
performed, after the two weight members 134 have been removed, the
above described second step, namely, a step in which the fibers 140
are arrayed individually so as to span the aligned concave rows 121
is performed for the concave rows 121 of the second layer of fiber
array flat plates 120. Thereafter, by again performing the third
step in the same manner, the temporary fixing step, if this is
necessary, and the fourth step, the second layer of fibers 140 can
be arrayed in predetermined positions.
[0215] Note that, in the arraying operation for each layer, it is
also possible after the fourth step has ended to perform a fiber
bonding step in which adhesive agent is put into the gaps between
the already tensioned fibers 140 and the concave rows 121 where
these tensioned fibers 140 are arrayed so as to bond the respective
fibers to the concave rows 121. This type of fiber bonding step can
also be performed for the respective fibers 140 and the concave
rows 121 of both of the fiber array flat plates 120 of each layer,
however, it is preferable that the other end 140b side of the
fibers 140 that are fixed by the fixing jig 163 is bonded to the
concave rows of the fiber array flat plates 120. The adhesive agent
that is used here is preferably one that can be easily removed
later from the fiber array flat plates 120, and examples thereof
include aqueous vinyl acetate based adhesive agents. By bonding the
other end 140b side of the fibers 140 that are fixed by the fixing
jig 163 to the concave rows of the fiber array flat plates 120,
when the work of inserting the curable resin solution is performed
in the subsequent fiber fixing step, resin solution can be
prevented from leaking from this bond portion.
[0216] In this manner, by repeating each of the above steps, the
fibers 140 are arrayed as far as the fifth layer, and the state
shown in FIG. 22 in which tension is imparted to all of the fibers
140 is obtained. Note that after the fifth layer, namely, the
topmost layer of the fibers 140 has been arrayed, then if another
fiber array flat plate is to be placed on top thereof (i.e., in the
third step), it is possible to stack spacers 131 in which no
concave rows have been formed instead of the fiber array flat
plate. A spacer 131 having sufficient strength is used for this
topmost stacked spacer 131, and the 5 stacked layers of fiber array
flat plates 120 are sandwiched by this spacer 131 and the base 133
of the positioning member 130. It is preferable if these are then
fastened with bolts or screws so that the stacked state of the
stacked fiber array flat plates 120 is maintained even in the
subsequent fiber fixing step and the fiber array is not disturbed.
Namely, it is preferable if the spacers 131 are used as presser
plates. Moreover, instead of the spacers 131 that are stacked on
the topmost layer as presser plates in this manner being fixed to
the base 133 of the positioning member 130, they can also be fixed
to the spacers 131 beneath the first layer of fiber array flat
plates 120 provided that the stacked state of the stacked fiber
array flat plates 120 is fixed.
[0217] In the above description, the third step to stack other
fiber array flat plates 120 is performed after the second step to
array fibers 140 and prior to the fourth step to impart tension to
these fibers 140. However, after the second step, it is also
possible to perform the third step after the fourth step has been
performed. In this case, it is preferable that, prior to the fourth
step, weight members 134, such as those used in the temporary
fixing step described above, whose contact surface with the fiber
array flat plates 120 is a flat surface are used to prevent the
respective fibers 140 from springing out from the concave rows 121
during the fourth step.
[0218] Next, the second embodiment of the fiber array step will be
described.
[0219] In the second embodiment as well, firstly, as is shown in
FIG. 23, the positioning through holes of two spacers 131 are
fitted respectively onto the two groups of supporting columns 132
of the positioning member 130, and the spacers 131 are put in
position. Next, one fiber array flat plate 120 is prepared, and the
positioning through holes 122 therein are fitted onto one group of
the supporting columns 132 of the positioning member 130. The fiber
array plate 120 is thus positioned in a predetermined position. The
above process makes up a first step.
[0220] Next, a second step is performed in which one other fiber
array flat plate 120 is prepared, and one end 140a of each fiber
140 that has been cut to a predetermined length is arrayed
individually in concave rows 121 and bonded, as is shown in FIG.
24, so that a fiber array flat plate 120' on which the fiber
bonding has already been completed is manufactured.
[0221] Here, the method used to bond the fibers 140 in the concave
rows 121 is preferably a method in which an adhesive agent is
thinly coated in advance in each concave row 121 and, thereafter,
the one end 140a side of each fiber 140 is arrayed in the concave
rows 121. At this time, care is taken that the adhesive agent does
not spill over into portions other than the concave rows 121 of the
fiber array flat plate 120, and if it does spill over, it is
necessary that it be removed immediately. If adhesive agent is
present in portions other than the concave rows 121 of the fiber
array flat plates 120, then it is not possible to stack other fiber
array flat plates 120 in a stable manner on top of this fiber array
flat plate 120' on which the fiber bonding has already been
completed. There is also a possibility that it will affect the
array pitch of the fibers in the fiber array body 150 that is
ultimately obtained.
[0222] Next, as is shown in FIG. 25, a third step is performed in
which the other end (i.e., the free end) 140b sides of the fibers
140 that were arrayed and bonded in the concave rows 121 in the
second step are arrayed individually in the concave rows of the
fiber array flat plate 120 that was stacked on the positioning
member 130 in the first step. The arraying operation here can be
easily performed because the one end 140a side of the fibers 140
has already been bonded to the concave rows 121.
[0223] Next, as is shown in FIG. 26, the fourth step is performed
in which another fiber array flat plate 120 is stacked on top of
the fiber array flat plate 120 that is already stacked on the
positioning member 130 so that the respective fibers 140 arrayed
here do not spring out from the concave rows 121.
[0224] After the fourth step and prior to the fifth step, it is
preferable that, as is shown in FIG. 27, a temporary fixing step is
performed in which a weight member 134 such as that described in
the first embodiment is placed on the fiber array flat plate 120
that was placed in a predetermined position in the fourth step, so
that the state of close contact between the fiber array flat plate
120 of the first layer (i.e., the bottom most layer) and the fiber
array flat plate 120 of the second layer is maintained. By
performing this temporary fixing the six arrayed fibers 140 do not
spring out from the concave rows, and the fifth step that is
performed next can be performed stably and with improved work
efficiency.
[0225] In the fifth step, as is shown in FIG. 28, the fiber array
flat plate 120' in which the fibers have already been bonded is
positioned a predetermined distance apart such that the concave
rows 121 that are formed in this fiber array flat plate 120' are in
alignment with the concave rows 121 of the fiber array flat plate
120 that has already been placed in a predetermined position. Next,
a weight member 134 is also preferably placed on top of the fiber
array flat plate 120' in which the fiber bonding has already been
completed.
[0226] Next, a sixth step is performed in which tension is imparted
to each of the arrayed fibers 140 to a degree that does not cause
the fibers 140 to be elastically deformed or to break.
[0227] In the sixth step, the same type of tension imparting device
160 as that used in the first embodiment is used and the same type
of method to impart the tension can be used, however, at this time,
the one end 140a side of the fibers 140 is already in a state of
being bonded to the fiber array flat plates 120' in which the fiber
bonding is completed, and, furthermore, these fiber array flat
plates 120' in which the fiber bonding is completed are fixed by
the supporting columns 132 so as not to move. Accordingly, because
the fibers 140 do not move even if tension is imparted thereto, in
the second embodiment, it is not necessary to fix the fibers 140
using the fiber fixing section 162, and the other end 140b side is
fixed in the fixing jig 163.
[0228] By performing each of the above described steps, the first
layer of fibers 140 can be arrayed in predetermined positions. By
then repeating the second and subsequent steps in the same manner,
the second and subsequent layers of fibers 140 can be arrayed in
predetermined positions.
[0229] Moreover, once the arraying of the fibers 140 has been
completed as far as the fifth layer, in the same way as in the case
of the first embodiment, it is preferable that a spacer 131 in
which no concave rows are formed and that can also act as a
pressing plate is placed on the topmost layer. This spacer 131 and
the base 133 of the positioning member 130 should then be fixed by
bolts or screws, so that the stacked state of the stacked fiber
array flat plates 120 is maintained and the array of fibers 140 is
not disturbed.
[0230] Furthermore, in the array operation for each layer, after
the sixth step has ended, as was described in the first embodiment,
it is also possible to perform a fiber bonding step in which the
respective fibers are bonded in the concave rows 121 by inserting
an adhesive agent between the fibers 140 that have already been
tensioned and the concave rows 121 where these tensioned fibers are
arrayed. Note that when this type of fiber bonding step is
performed, it is performed on the other end 140b side of the fibers
140 that are fixed by the fixing jig 163.
[0231] In the above description concerning the second embodiment,
the fourth, fifth, and sixth steps are performed in sequence on the
other end 140b side of the bonded fibers 140 after the third step
in which the fibers are arrayed individually in the concave rows
121 of the fiber array flat plate 120 that has already been placed
in a predetermined position, however, it is also possible to
perform the fourth step after the third and then the fifth steps
have been performed, or after the third and then the fifth and
sixth steps have been performed. In this case, it is preferable
that the respective fibers 140 are prevented from springing out
from the concave rows 121 during the fifth and sixth steps by using
a weight member 134 such as that used in the first embodiment.
[0232] Note that a method that employs a winding mechanism 170 such
as that shown in FIGS. 29A and 29B may be used as a method for
efficiently manufacturing the fiber array flat plate 120' shown in
FIG. 24 in which the fiber bonding has already been completed,
namely, as a method for efficiently implementing the second step of
the second embodiment.
[0233] This winding mechanism 170 is equipped with a fiber winding
drum 171 that rotates around a shaft 171a in the direction of the
arrow in FIG. 29B. By continuously supplying fiber 140 from a
bobbin 172 to this fiber winding drum 171, the fiber 140 is wound
onto the fiber winding drum 171. The winding mechanism 170 is also
provided with a movable unit 173 that moves along a movement shaft
173a that is provided in parallel with the shaft 171a of the fiber
winding drum 171. A first rotation guide 174 and a fiber guide
nozzle 175 are fixed to this movable unit 173. The symbols 176 and
177 in the drawings respectively indicate a second rotating guide
and a third rotating guide.
[0234] The symbol 178 in the drawings indicates a dancer rotating
guide. By moving in a vertical direction in the drawings, the
dancer rotating guide 178 applies a constant tension that is not
more than a yield load to the fibers 140 such that the fibers 140
do not sag.
[0235] Specifically, a braking force is placed on the supply of
fibers 140 from the bobbin 172 such that the position of the dancer
rotating guide 178 is kept constant. Namely, constant feedback is
made to a brake (not shown) provided in the bobbin 172 as to the
position in a vertical direction of the dancer rotating guide 178,
and the brake is loosened when the dancer rotating guide 178 rises
up and is tightened when the dancer rotating guide 178 drops down.
In addition to this, it is also possible to keep a constant tension
using a tension detector that generates electrical signals
corresponding to the tension acting on the fibers 140 being
supplied.
[0236] When this type of winding mechanism 170 is used to
manufacture the fiber bonded fiber array flat plate 120' by
individually arraying and bonding the one end 140a side of the
fibers 140 that have been cut to predetermined lengths in the
concave rows 121 of the fiber array flat plates 120, firstly, a
curable adhesive agent that has no effect on the material of the
fibers 140 is coated in advance onto the concave rows 121 of a
fiber array flat plate 120. Next, this fiber array flat plate 120
is fixed onto the drum face of the fiber winding drum 171 such that
the concave rows 121 are orthogonal to the shaft 171 a of the fiber
winding drum 171, and such that the surface on the side thereof
where the concave rows 121 are not formed is in contact with the
drum face. Fiber 140 is then supplied from the bobbin 172 to the
fiber winding drum 171 via the second rotating guide 176, the
dancer rotating guide 178, the third rotating guide 177, the first
rotating guide 174, and the fiber guide nozzle 175 in that
sequence, and the distal end of the fiber 140 is fixed to the drum
face.
[0237] Next, the fiber winding drum 171 is continuously rotated in
the direction shown by the arrow, and each time the fiber winding
drum 171 rotates, the movable unit 173 is moved the same distance
as the distance between adjacent concave rows 121 in one direction
(i.e., the direction indicated by the arrow in FIG. 29A) along the
shaft 171 a of the fiber winding drum 173, and the fiber guide
nozzle 175 that is fixed to the movable unit 173 is also moved in
concert therewith.
[0238] By employing this structure, fibers are individually arrayed
in sequence in all of the concave rows 121 starting from a concave
row 121 positioned furthest to one end of the plurality of concave
rows 121 of the fiber array flat plate 120 that is mounted on the
fiber winding drum 171.
[0239] After fibers have been arrayed in all of the concave rows,
the arrayed fibers 140 are cut off outside the fiber array flat
plate 120. Consequently, a fiber array flat plate 120' in which the
fiber bonding has been completed can be removed from the fiber
winding drum 171.
[0240] Note that the curable adhesive agent that is coated here in
advance in the concave rows 121 is a highly viscous adhesive agent
whose curing speed is comparatively slow. If the concave rows 121
are coated with this type of adhesive agent, the fibers 140 are
adhered by the viscosity of the adhesive agent. Accordingly, the
adhesive agent can be cured after the fiber bonded fiber array flat
plate 120' has been removed from the fiber winding drum 171.
[0241] In addition to this, it is also possible to use an
ultraviolet curable adhesive agent for the curable adhesive agent.
In this case, after fibers 140 have been arrayed in all of the
concave rows 121, the adhesive agent is cured by ultraviolet light
irradiation prior to the fibers 140 being cut. Thereafter, the
fiber bonded fiber array flat plates 120' may be removed from the
fiber winding drum 171.
[0242] The method used to coat the concave rows 121 of the fiber
array flat plates 120 in advance with these curable adhesive agents
may be a method in which the concave rows 121 are coated with the
adhesive agents by hand. However, it is also possible to provide a
roll coater or dispenser on the winding mechanism 170 so that the
fiber 140 supplied from the bobbin 172 or the concave rows 121 of
the fiber array flat plate 120 that is fixed to the fiber winding
drum 171 can be automatically coated with adhesive agent.
[0243] In the winding mechanism 170 of this example, by moving the
movable unit 173 in order to array fibers 140 in sequence in the
plurality of concave rows 121, the fiber guide nozzle 175 that is
fixed to the movable unit 173 moves uniformly along the shaft 171 a
of the fiber winding drum 171, however, it is also possible to not
move the fiber guide nozzle 175, and, instead, to move the fiber
winding drum 171 uniformly along the shaft 171a.
(Fiber Fixing Step)
[0244] In the method of manufacturing the fiber array body of the
present invention, after the above described fiber array step, a
fiber fixing step is performed in which the fibers 140 that were
arrayed three-dimensionally in the fiber array step are fixed as
they are without any further modification. A description will now
be given of a fiber fixing step using as an example a method in
which spaces between three-dimensionally arrayed fibers 140 are
filled with curable resin which is then cured.
[0245] Firstly, as is shown in FIG. 30, by performing the fiber
array step, 30 fibers 140 are arrayed in their respective concave
rows and tension is imparted thereto. A potting block 190 is then
placed so as to enclose portions of these fibers 140 that are
suspended between two stacked objects 180a and 180b that are
obtained by stacking the fiber array flat plates 120 in five
layers.
[0246] In this example, as is shown in FIG. 31, the potting block
190 is formed in a cylindrical shape by combining four plate shaped
block pieces 190a, 190b, 190c, and 190d in the manner shown in the
drawing.
[0247] The four block pieces 190a, 190b, 190c, and 190d of this
example are formed from a metal such as aluminum, and release
processing is performed on those surfaces of the block pieces that
come into contact with each other and on those surfaces of the
block pieces that form interior wall surfaces when the four pieces
are combined into a cylinder shape. Examples of the method used to
perform this release processing include a method in which, as is
shown in the drawings, a sheet-shaped object 191 formed from highly
non-adhesive Teflon (registered trademark), polyethylene, or
polypropylene or the like is adhered onto each surface, as well as
a method in which a coated resin membrane is formed by coating
these resins on each surface. If release processing is preformed in
this manner, then after a curable resin solution is later poured
inside the potting block 190 and is then cured, the potting block
190 can be easily released from the cured resin. Moreover, instead
of performing this release processing on the block pieces 190a,
190b, 190c, and 190d, it is also possible to form the potting block
itself from a highly non-adhesive resin.
[0248] A semi-conical notch 192 that becomes wider towards one end
thereof is formed in one surface of the inner wall surfaces of the
cylindrical potting block 190. As is described below in detail,
this notch 192 forms a filling aperture when a curable resin is
poured into the potting block 190 so as to fill it. Note that, in
FIG. 31, in order to make the configuration of the potting block
190 easier to understand, the fasteners used to fix the potting
block 190, the 30 fibers, and the tension imparting device and the
like are omitted from the drawing. The 30 fibers, in actual fact,
extend in a left-right direction in the drawing inside a hollow
portion of the potting block that is indicated by the symbol
193.
[0249] As is shown in FIG. 30, the potting block 190 that is made
up of the four block pieces 190a, 190b, 190c, and 190d is fixed by
fasteners 194 such as bolts or screws so as to enclose the 30
fibers 140, and so that the one end of the potting block 190 where
the filling aperture is not formed is in close contact with the one
stacked object 180a of fiber array flat plates 120. At this time, a
sealing member 195 formed from silicon rubber or the like that has
peelability and elasticity is interposed so that the curable resin
solution that is supplied later does not leak out from the close
contact portion between the potting block 190 and the stacked
object 180a.
[0250] After this, as is shown in FIG. 32, the potting block 190 is
stood upright together with the 30 fibers 140, the fiber array jig
110, and the tension imparting device 160 such that the end of the
potting block 190 on the side where the filling aperture is formed
(i.e., the aperture end) is positioned facing upward.
[0251] A spout of a cup 196 that contains curable resin solution is
placed against the filling aperture that is formed in the potting
block 190 by the semi-conical notch 192, and the curable resin
solution is poured into the hollow portion 193 of the potting block
190 so as to spread along the internal wall surfaces of the potting
block 190. Subsequently, the potting block 190 is left undisturbed
at a predetermined temperature for a predetermined length of time
so that the supplied curable resin solution is able to cure.
[0252] The method used to fill the interior of the potting block
190 with the curable resin solution may also be a method such as
that shown in FIG. 33.
[0253] Namely, a resin pouring aperture that is used to pour in
resin is formed in a side wall of the potting block 190 in the
vicinity of one end on the side that is blocked by being placed in
tight contact with the stacked object 180a. Next, a tube 198 is
prepared and one end of this tube 198 is inserted into the resin
pouring aperture. The other end of the tube 198 is connected to a
funnel 199. By then pouring curable resin solution into the funnel
199, the curable resin solution gradually fills the interior of the
potting block 190 from bottom to top.
[0254] Note that when the curable resin solution is being used in
this manner, it is preferable that the curable resin solution is
stirred and degassed in advance in a vacuum. If it is degassed,
there are no air gaps inside the resin after it has cured and the
resin sufficiently permeates the space between the fibers 140. It
is even more preferable if the curable resin solution is
sufficiently degassed and if the above described resin pouring task
is conducted under reduced pressure.
[0255] After the curable resin solution with which the interior of
the potting block 190 has been filled has cured, the potting block
190 is disassembled into the four block pieces 190a, 190b, 190c,
and 190d. The fiber array body 150 that is made up of the 30 fibers
140 and the curable resin 151 that fixes the fibers 140 is
separated from the tension imparting device 160 and the respective
fiber array flat plates 120. By then cutting the fibers 140 as is
appropriate, a fiber array body 150 in a state such as that shown
in FIG. 16, or in a state such as that shown in FIG. 34 or FIG. 35
can be obtained.
[0256] The type of curable resin that is used here is preferably a
curable resin solution that is in a low viscosity state at normal
temperature and that is able to fill the hollow portion 193 of the
potting block 190 and then cure at room temperature, and that after
curing is able to be sliced easily by a cutter or the like into
thin pieces having a uniform thickness. Furthermore, the obtained
thin pieces should preferably have sufficient hardness and
elasticity that they do not become chipped or broken. Examples of
this type of curable resin include two-liquid reaction curable
resins such as urethane resins.
(Fiber)
[0257] A description has been given above of a fiber array step in
which a plurality of fibers 140 are arrayed three-dimensionally,
and a fiber fixing step in which the three-dimensionally arrayed
fibers 140 are fixed. There is, however, no particular restriction
as to the type of fiber that is arrayed and then fixed in the
manner described above. Examples thereof include chemical fibers
such as synthetic fibers, semisynthetic fibers, regenerated fibers,
and inorganic fibers as well as natural fibers.
[0258] Representative examples of synthetic fibers include: various
types of polyamide based fibers such as nylon 6, nylon 66, and
aromatic polyamides; various types of polyester based fibers such
as polyethylene terephthalate, polybutylene terephthalate,
polylactic acids, and polyglycolic acids; various types of acrylic
based fibers such as polyacrylonitrile; various types of polyolefin
based fibers such as polyethylene and polypropylene; various types
of polyvinyl alcohol based fibers; various types of polyvinylidene
chloride based fibers; various types of polyvinyl chloride based
fibers and polyurethane based fibers; phenol based fibers; fluorine
based fibers such as polyvinylidene fluoride and
polytetrafluoroethylene; polyalkylene paraoxybenzoate based fibers;
fibers that use (meth)acrylic based resins such as polymethyl
methacrylate; and fibers that use polycarbonate based resins.
[0259] Representative examples of semisynthetic fibers include:
various types of fibers that are based on cellulose based
derivatives that use diacetate, triacetate, chitin, or chitosan as
a raw material; and various types of protein based fibers that are
known as promix.
[0260] Representative examples of regenerated fibers include
various types of cellulose based regenerated fibers such as rayon,
cupra, and polynosic that are obtained using a viscose method, a
copper-ammonia method, or an organic solvent method.
[0261] Representative example of inorganic fibers include glass
fibers, and carbon fibers.
[0262] Representative examples of natural fibers include: vegetable
fibers such as cotton, flax, ramie, and jute; animal fibers such as
wool and silk; and mineral fibers such as asbestos.
[0263] These fibers 140 can be used as is appropriate in the
manufacturing of the fiber arrayed bodies 150, however, as is
described above, because tension is imparted to the fibers 140 in
the fiber array step, of the fibers that are described above,
polycarbonate based fibers, polyester based fibers, nylon based
fibers, and aromatic polyamide fibers and the like that have a high
modulus of elasticity and yield strength are preferably used.
[0264] Any fibers other than natural fibers that are obtained from
a known fiber forming technology such as a melt spinning method, a
wet spinning method, and a dry spinning method, or from a
combination of these technologies can also be used.
[0265] Furthermore, unprocessed fibers may be used without any
modification thereto for the fibers 140, however, if necessary,
fibers into which a reactive functional group has been introduced
may be used, or fibers that have undergone plasma processing or
irradiation processing using .gamma.-rays or electron beams or the
like may be used.
[0266] Moreover, there is no particular restriction as to the form
of the fibers 140, and they may be in monofilament form or in
multifilament form. In addition, the fibers 140 may be formed by
spun yarn obtained by spinning short fibers. The fibers 140 may
also be hollow fibers or fibers having a porous structure. Hollow
fibers can be manufactured using a known method that employs
special nozzles.
[0267] There is no particular restriction as to the outer diameter
of the fibers 140 and fibers 140 having the desired outer diameter
can be used. However, if the outer diameter is too small, breakages
tend to occur and there is a deterioration in the ease of handling.
On the other hand, the smaller the outer diameter of the fibers
140, the higher the density at which the fibers 140 are able to be
arrayed. Accordingly, the outer diameter of the fibers 140 is set
so as to provide both ease of handling and the desired arrayed
density. Preferably, the outer diameter of a single fiber is 500
.mu.m or less, and more preferably 300 to 100 .mu.m. If a
multifilament fiber is used for the fibers 140, then 83 dtex/36
filament or 82 dtex/45 filament or the like can be used without any
modification.
[0268] For example, as is described below, a monofilament fiber
having an outer diameter of 150 .mu.m is used for the fibers 140
when an organism related substance fixed microarray is being
manufactured from the fiber array body 150. When this monofilament
fiber is arrayed at an array pitch of 200 .mu.m, the number of
fibers 140 that can be arrayed inside a 1 cm.sup.2 square is 2400.
Accordingly, by fixing one type of organism related substance in
one single fiber, it is possible to fix 2400 types of organism
related substance in each square centimeter. Moreover, if
monofilament porous fibers, monofilament hollow fibers or
monofilament porous hollow fibers having an outer diameter of
approximately 200 .mu.m are arrayed at an array pitch of 300 .mu.m,
a fiber array body 150 in which approximately 1000 fibers 140 are
arrayed in each square centimeter can be obtained. Accordingly, by
fixing one type of organism related substance in one single fiber,
it is possible to fix 1000 types of organism related substance in
each square centimeter.
[Method of Manufacturing an Organism Related Substance Fixed
Microarray]
[0269] Next, a description will be given of a method of
manufacturing an organism related substance fixed microarray from a
fiber array body 150 obtained by performing the above described
fiber array step and fiber fixing step.
[0270] In the fiber array step and fiber fixing step, if a fiber in
which an organism related substance has previously been fixed is
used as the three-dimensionally arrayed and fixed fiber 140, then
by slicing the fiber array body 150 that is obtained, such as that
shown in FIG. 16, into thin pieces in a direction intersecting the
fibers 140, as is shown in FIG. 36, the fibers 140 in which
organism related substance has been fixed are fixed by curable
resin, and thin slices of an organism related substance fixed
microarray 200 can be obtained on both surfaces of which is exposed
a cross-section of the fibers 140. The direction of the slices
should be a direction that intersects the longitudinal direction of
the fibers 140. Preferably, it should be a direction that is
perpendicular to the longitudinal direction of the fibers 140.
[0271] If the organism related substance fixed in the fibers 140
is, for example, a nucleic acid, then by providing a specimen for
the obtained organism related substance fixed microarray 200 and
performing hybridization, it is possible to detect a specific
nucleic acid array present in the specimen using the nucleic acid
fixed to the fibers as a probe.
[0272] Note that if a multifilament fiber or spun yarn or the like
is used for the fibers 140, then it is possible to fix organism
related substance in the gaps between the individual fibers.
Moreover, if a hollow or porous fiber is used for the fibers 140,
then it is possible to fix organism related substance in the hollow
portions or in the gaps within the fibers 140.
[0273] If, on the other hand, in the fiber array step and fiber
fixing step, a fiber in which an organism related substance has not
previously been fixed is used as the three-dimensionally arrayed
and fixed fiber 140, then a fiber array body 150 is obtained in the
state shown in FIG. 34 or FIG. 35, namely, in a state in which at
least one end of the fibers 140 extends beyond the curable resin
151 , and after the organism related substance has been fixed in
each fiber 140 of this fiber array body 150, the fiber array body
150 is sliced into thin pieces in a direction intersecting the
fibers 140.
[0274] An example of a method used to fix organism related
substance in the respective fibers 140 of the fiber array body 150
shown in FIG. 34 in which fibers 140 in which organism related
substance has not been fixed are arrayed is the method shown in
FIG. 37. This method is effective when porous fibers, hollow
fibers, or porous hollow fibers are used for the fibers 140 that by
reducing the pressure at one end of the fibers allow a liquid to be
suctioned from the other end of the fibers.
[0275] Firstly, the same number of containers 197 as the number of
the fibers 140, namely, in this case 30 containers 197 are
prepared, and a solution that contains an organism related
substance is placed inside each container 197. The ends of the
fibers 140 that extend from the curable resin 151 of the fiber
array body 150 are immersed individually into the containers 197
containing the solution. By then suctioning the solution from the
other end of the fibers 140, the solution containing the organism
related substance in the hollow portion or porous portion of each
fiber 140 is suctioned up and the organism related substance can be
introduced into each fiber 140. The type of organism related
substance that is introduced into each fiber 140 may be different
in every single one of the 30 fibers 140. It is also possible to
group together a plurality of fibers and introduce the same type of
organism related substance into that group.
[0276] Examples of the organism related substance that is
introduced into the fibers 140 in this manner include nucleic acids
such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA),
peptide nucleic acid (PNA), and oxypeptide nucleic acid (OPNA) as
well as proteins and polysaccharides. The organism related
substance used may be one that is commercially available, or one
that is obtained from living cells.
[0277] If a nucleic acid is used as the organism related substance,
the DNA or RNA from living cells may be prepared using a known
method. For example, DNA may be extracted using Blin's method (see
Blin et. Al., Nucleic Acids Res. 3: 2303 (1976)). RNA may be
extracted using Favaloro's method (see Favaloro et. Al., Methods
Enzymol. 65: 718 (1980)).
[0278] It is also possible to use chain or toroidal plasmid DNA or
chromosome DNA, DNA pieces obtained by slicing these using
restriction enzymes or by chemically slicing them, DNA that has
been synthesized by enzymes in a test tube, or else chemically
synthesized DNA.
[0279] These various organism related substance types may be used
unmodified as they are, or they may be used in the form of
derivatives in which the organism related substance has undergone
chemical modification, or, if necessary, they may transformed and
then used. For example, if a nucleic acid is used for the organism
related substance, then amino formation, biotin formation,
digoxigenin formation and the like, which are known as methods for
chemically modifying organism related substance (Current Protocols
in Molecular Biology, Ed.; Frederick M. Ausubel et. al. (1990) and
Deisotoping Experimental Protocols (1) DIG Hybridization
(Shuujunsha)), can be employed.
[0280] After the organism related substance has been introduced
into the fibers 140, the method that is used to fix it therein is
able to utilize the various types of chemical or physical
interaction between the fibers 140 and the organism related
substance, namely the chemical or physical interaction between the
functional groups belonging to the fibers 140 and the constituents
forming the organism related substance.
[0281] If porous fibers, hollow fibers, or porous hollow fibers are
used for the fibers 140, then after the solution that contains the
organism related substance has been suctioned and introduced into
the hollow portion or porous portion of the fibers 140 constituting
the fiber array body 150 using the above described method or the
like, the organism related substance can be fixed to these fibers
140 using the interaction between functional groups present on the
internal wall surfaces and the like of the hollow portions or
porous portions of the fibers 140 and the constituents making up
the organism related substance.
[0282] If an unmodified nucleic acid is fixed to the fibers 140,
then, after the nucleic acid and the fibers 140 have interacted,
they can be fixed by baking or ultraviolet light irradiation. If a
nucleic acid modified by an amino group is fixed to the fibers 140,
then this can be coupled with functional groups of the fibers using
a cross linking agent such as glutaraldehyde or
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Furthermore,
it is also possible to transform the fixed organism related
substance by performing heat processing, alkaline processing,
surfactant processing or the like. If organism related substance
obtained from raw material such as cells or biomass is used, then
it is also possible to perform processing such as removing
unnecessary cell components. Note that these processings may be
performed separately or may be performed simultaneously. Moreover,
the organism related substance may be fixed in the fibers 140 after
these processings have been performed on samples containing the
organism related substance.
[0283] As has been described above, when a plurality of fibers 140
are being arrayed three-dimensionally, the fiber array jig 110 that
is used has a plurality of fiber array plates 120 on one surface of
which are formed substantially in parallel with each other a
plurality of concave rows 121 in each one of which is arrayed a
single fiber 140, and has a positioning member 130 that is used to
place these fiber array plates 120 in predetermined positions. At
least two of the fiber array flat plates 120 are positioned apart
from each other by the positioning member 130 such that the concave
rows 121 formed in each fiber array flat plate 120 are in alignment
with each other, and one or more of the other fiber array flat
plates 120 are stacked one by one on top of these fiber array flat
plates 120. As a result, the fibers 140 can be arrayed at a high
density, with a high degree of accuracy, and extremely efficiently,
and it also becomes possible to mass produce the fiber array bodies
150 for industry. Namely, if this type of fiber array jig 110 is
used, it is not necessary to perform the complex task of inserting
individual fibers through holes formed in a jig, as is the case
conventionally. Moreover, because it is not necessary to guide the
fibers being inserted into the holes using forceps or the like, the
problem of fibers that have already being inserted into adjacent
holes obstructing the operation when inserting fibers using forceps
does not arise. In addition, because the operation is not one of
inserting the fibers 140 into holes, but of arraying them in the
concave rows 121, even if the outer diameter of the fibers is
narrow and they have low rigidity, they can be arrayed easily so
that a greater degree of density in the array of the fibers 140
becomes possible.
[0284] Moreover, when this type of fiber array jig 110 is used, the
work involved in the fiber array step can be divided so that, from
this viewpoint as well, the productivity of the fiber array body
150 is improved.
[0285] For example, if the above described fiber array step is
performed using the second embodiment, then the task can be divided
into a step in which fiber bonded fiber array flat plates 120' can
be continuously manufactured in large volume using the winding
mechanism 170 shown in FIGS. 29A and 29B, and all steps other than
this step. As a result, different operators are able to advance the
work simultaneously. In contrast, in work in which the fibers are
inserted one by one in a jig in which holes are formed, as is the
case conventionally, the entire task of inserting all of the fibers
in sequence is just one step and it is difficult for the labor
involved therein to be divided. As a result, the work efficiency is
poor.
[0286] Namely, by using the fiber array jig 110 described above,
even if the outer diameter of the fibers 140 is small and they are
difficult to handle, they can still be arrayed accurately at a high
density and also efficiently, and mass production of the fiber
arrayed bodies is possible because the manufacturing tasks can be
performed separately. As a result, it is also possible to mass
produce organism related substance fixed microarrays that enable a
large variety of samples to be analyzed.
EXAMPLES
[0287] The present invention will now be described specifically
using the examples given below.
Reference Example 1
[0288] Probe A and probe B below were synthesized. TABLE-US-00001
Probe A gcgatcgaaa ccttgctgta cgagcgaggg ctc (array number 1) Probe
B gatgaggtgg aggtcagggt ttgggacagc ag (array number 2)
[0289] The synthesis of the oligonucleotides was performed using an
automatic DNA/RNA synthesizer (model 1394) manufactured by PE
Biosystems. In the final step of the DNA synthesis, an aminohexyl
group [NH.sub.2(CH.sub.2).sub.6--] was introduced into the 5'
terminal of the respective nucleotides using an aminolink II (trade
name--manufactured by Applied Biosystems).
Reference Example 2
[0290] A solution A formed from the composition described below was
prepared. PMMA monoacrylate (molecular weight 6000): 5 parts by
mass Toluene: 95 parts by mass
Reference Example 3
[0291] A solution B formed from the composition described below was
prepared. [0292] Acrylamide: 9 parts by mass [0293] N,N'-methylene
bisacrylamide: 1 part by mass [0294]
2,2'-azobis(2-methylpropionamidine)dihydrochloride (V-50): 0.1
[0295] parts by mass [0296] water: 90 parts by mass
Example 1
[0296] (1) Introduction and Fixing of Organism Related Substance in
A Hollow Fiber
[0297] A hollow fiber made out of nylon (i.e., a melt spun product
made of nylon 6 having an outer diameter of 0.28 mm, and an inner
diameter (i.e., the diameter of the hollow portion) of 0.2 mm) was
cut into 700 mm lengths so that 900 nylon hollow fibers were
prepared. Formic acid was suctioned from one end of these hollow
fibers into the hollow portion thereof and was held therein for one
minute. Next, a large volume of water at room temperature was
poured into the hollow portions so that the hollow portions were
properly washed, and they were then dried. This constituted the
preprocessing of the nylon hollow fibers.
[0298] The oligonucleotide probe A and probe B having amino groups
that were synthesized in Reference example 1 were fixed to the
internal walls of the nylon hollow fibers that had undergone
preprocessing. Specifically, a solution obtained by adding probe A
to a potassium phosphate buffer solution was introduced via one end
portion of 450 hollow fibers, while a solution obtained by adding
probe B to a potassium phosphate buffer solution was introduced via
one end portion of the other 450 hollow fibers. These were then
kept overnight at 20.degree. C.
[0299] Thereafter, interior portions of the nylon hollow fibers
were washed in a potassium phosphate buffer solution and a
potassium chloride aqueous solution, so that nylon hollow fibers to
which organism related substance was fixed were obtained with probe
A being fixed to the internal wall surfaces of 450 hollow fibers
and probe B being fixed to the internal wall surfaces of 450 hollow
fibers.
[0300] (2) Manufacturing of Hollow Fiber Array Body to which
Organism Related Substance has been Fixed
(i) Fiber Array Step
[0301] A fiber array step was performed following the first
embodiment that was described using FIGS. 17 to 22, so that 900
nylon hollow fibers to which organism related substance had been
fixed were arrayed in 30 rows multiplied by 30 layers.
[0302] Specifically, 60 flat plates made of SUS 304 spring steel
having a width of 30 mm, a length (i.e., the direction of the
concave rows) of 10 mm, and a thickness of 0.42 mm, and in which 30
concave rows 121 having a width of 0.3 mm and a depth of 0.3 mm
were formed in parallel at a pitch of 0.42 mm, and in which
positioning through holes 122 having a diameter of 4 mm were formed
in the vicinity of the two side ends (i.e., in the transverse
direction) thereof were used as the fiber array flat plates 120 of
the fiber array jig 110.
[0303] Two groups (with two columns in each group) of supporting
columns 132 were erected on a base 133 made from a rectangular flat
plate, and this was used as a positioning member 130 for
positioning the above fiber array flat plates 120 in predetermined
positions. Note that the gap between one group of supporting
columns and the other group of supporting columns was 150 mm.
[0304] In addition, flat plates that had a thickness of 15 mm and
that, apart from the fact that concave rows were not formed
therein, were the same size as the fiber array flat plates 120, and
in which the positioning through holes were formed in the same
manner were prepared as spacers 131.
[0305] Note that nylon hollow fibers having probe A fixed to the
internal walls thereof and nylon hollow fibers having probe B fixed
to the internal walls thereof were arrayed in parallel
alternatingly in the concave rows 121 of each fiber array flat
plate 120. In addition, a temporary fixing step was performed for
each layer using 1 kg weight members 134.
[0306] The tension imparting device 160 shown in FIG. 21 was used
to impart tension to each fiber, and tension was imparted such that
a load of 15N acted on each nylon hollow fiber, and each fiber was
pulled such that there was no sagging in any of the fibers.
[0307] Furthermore, in the task of arraying each layer, after the
fourth step had ended, a fiber bonding step was performed in which
the weight member 134 on the fixing jig 163 side and the fiber
array flat plate 120 beneath it are temporarily removed, and the
respective fibers are bonded to the concave rows 121 by coating an
adhesive agent between the hollow fibers and the concave rows 121
where these hollow fibers are arrayed. A water soluble vinyl
acetate based adhesive agent ("Fast Dry" used for bonding wood:
Konishi (Ltd.)) was used for the adhesive agent, and this was
smeared on so as to sufficiently cover the spaces between the
adhesive agent, the concave rows, and the hollow fibers using a
squeegee equipped with a urethane blade. After the adhesive agent
was smeared on in this manner, the fiber array flat plate 120 and
the weight member 134 were put back in place and pressure was
applied for several seconds at a load of approximately 200N.
[0308] After the 30th layer of fibers was arrayed, then if another
fiber array flat plate is to be placed on top thereof (i.e., in the
third step), a spacer 131 in which no concave rows have been formed
can be stacked instead of the fiber array flat plate and used as a
presser plate. Namely, the spacer 131 that is stacked on the
topmost layer is fixed by screws to the base 133 of the positioning
member 130.
(ii) Fiber Fixing Step
[0309] As is shown in FIG. 32, the hollow portion 193 of the
potting block 190 was filled with a curable resin solution.
[0310] Specifically, two aluminum plates (a) having a thickness of
11.1 mm, a width of 50 mm, and a length of 100 mm and two aluminum
blocks (b) having a thickness of 19.5 mm, a width of 14.8 mm, and a
length of 100 mm making a total of four pieces were used for the
potting block 190. Release processing was performed on the potting
block 190 using Teflon (registered trademark) adhesive tape
(Nitoflon adhesive tape: manufactured by Nitto Denko (Ltd.)) having
a thickness of 0.13 mm and a width of 50 mm. Namely, Teflon
(registered trademark) adhesive tape was stuck onto the surfaces
(i.e., the surfaces having a width of 50 mm and a length of 100 mm)
of the aforementioned two aluminum plate (a) pieces and onto the
three surfaces (i.e., three of the four surfaces having a thickness
of 19.5 mm and a length of 100 mm) of the aforementioned two
aluminum block (a). Note that a filling aperture that is formed by
a semi-conical notch 192 is formed at one end of one surface of one
of the aluminum plates (a) and Teflon (registered trademark)
adhesive tape is stuck onto this surface.
[0311] These four pieces were then combined in the manner shown in
FIG. 31 so as to enclose the 30 rows by 30 layers of organism
related substance fixed nylon hollow fibers arrayed in the above
described (i), and a 20 mm.times.20 mm.times.100 mm hollow portion
193 was formed by the potting block 190. Note that silicon packing
having a thickness of 1 mm was used as the sealing member 195 that
was interposed such that the supplied curable resin solution did
not leak from the portion of tight contact between the potting
block 190 and the stacked object 180a. The silicon packing was the
same shape as the end surface of the potting block 190 and, in the
same way, is provided with a 20 mm.times.20 mm aperture portion of
which a portion was cut open. This cut open portion was opened up
and arranged so as to span across the 30 rows by 30 layers of nylon
hollow fibers. In addition, the stacked object 180a and the potting
block 190 were fastened together under pressure by the fasteners
194 in the form of screws.
[0312] A two-solution polyurethane resin (curing agent: Nipporan
4276, main agent: coronate 4403 with two parts by mass of carbon
black as an additive, mixture proportion: curing agent 38 parts by
mass to main agent 62 parts by mass, manufactured by Japan
Polyurethane Industries (Ltd.)) that had been degassed by being
stirred and mixed in a vacuum was poured from the cup 196, as is
shown in FIG. 32, into the hollow portion 193 of the potting block
190 along internal wall surfaces of the potting block 190.
[0313] In this state, after the resin was cured by being kept at
room temperature for 16 hours, the potting block 190 was
disassembled into four pieces, and a fiber array body made of nylon
hollow fibers having the configuration shown in FIG. 16 (i.e.,
having 30 rows by 30 layers) was obtained in which gaps between the
nylon hollow fibers were filled with polyurethane resin, and whose
cross-sectional dimensions were 20 mm.times.20 mm.times.length of
80 mm, and in which organism related substance was fixed to the
interior walls.
[0314] In addition, by slicing this fiber array body in thin pieces
having a thickness of 0.5 mm, approximately 140 organism related
substance fixed microarrays were obtained.
Example 2
(1) Manufacturing of Hollow Fiber Array Body to which Organism
Related Substance has not been Fixed
(i) Fiber Array Step
[0315] A fiber array step was performed following the second
embodiment that was described using FIGS. 23 to 30, so that 900
polycarbonate hollow fibers to which organism related substance had
not been fixed were arrayed in 30 rows by 30 layers.
[0316] Specifically, the same fiber array jig 110 as in Example 1
was used, and fibers were bonded in the respective concave rows 121
of 30 of the fiber array flat plates 120 thereof so that 30 fiber
bonded fiber array flat plates 120' in which 30 fibers were bonded
were prepared. The winding mechanism 170 shown in FIGS. 29A and 29B
was used in the preparation of the 30 fiber bonded fiber array flat
plates 120'. Namely, fiber array flat plates 120 the concave rows
121 of which had been coated with a water soluble vinyl acetate
based adhesive agent ("Fast Dry" used for bonding wood: Konishi
(Ltd.)) were fixed to the fiber winding drum (having a diameter of
320 mm) 171 of the fiber winding mechanism 170 shown in FIGS. 29A
and 29B. Polycarbonate hollow fibers (i.e., a melt spun product
made of polycarbonate with an additive of one part by mass of
carbon black and having an outer diameter of 0.28 mm, and an inner
diameter of the hollow portion of 0.16 mm) were then unwound from
the bobbin 172 onto which they were wound such that tension of 0.1
N was acting thereon, and were consecutively inserted into the 30
concave rows 121 of the fixed fiber array flat plates 120.
[0317] Next, the adhesive agent that was squeezed out from the
concave rows 121 by the insertion therein of the polycarbonate
hollow fibers was spread fully over the concave rows 121 by a
squeegee equipped with a urethane blade, and excess adhesive agent
was totally removed. Thereafter, the polycarbonate hollow fibers
were cut at a portion thereof 30 cm distant from the fiber array
flat plates 120 in parallel with the shaft 171a of the fiber
winding drum 171, and the fiber bonded fiber array flat plates 120'
were removed from the fiber winding drum 171. The fiber bonded
fiber array flat plates 120' that were obtained were then stored in
a suspended state using the positioning through holes formed in the
fiber bonded fiber array flat plates 120' such that the
polycarbonate hollow fibers did not become entangled with each
other.
[0318] This operation was then repeated 30 times. As a result, 30
polycarbonate hollow fiber bonded fiber array flat plates 120' in
which 30 polycarbonate hollow fibers were bonded in the concave
rows 121 were obtained.
[0319] PMMA monoacrylate was then introduced into the internal
walls of each hollow fiber of the 30 fiber bonded fiber array flat
plates 120' that were obtained.
[0320] Specifically, one end of each of the 30 polycarbonate fibers
of the fiber bonded fiber array flat plates 120' was immersed in a
semi cylindrical container containing the solution A prepared in
Reference example 2. The other end of the 30 polycarbonate fibers
were first aligned in parallel with the adhesive agent side of a
silicon tape having a width of 20 mm, a length of 50 mm, and a
thickness of 1 mm and having an adhesive agent provided on one side
thereof. The fibers were then wound onto the tape in a columnar
shape in their longitudinal direction and were cut in a
substantially perpendicular direction relative to the fibers in a
central portion in the longitudinal direction of the columnar
shape. As a result, end surfaces of the 30 hollow fibers were
exposed. Next, these end surfaces were press-inserted respectively
into one end of polycarbonate pipes having an inner diameter
smaller than the diameter of the end surfaces. The other ends of
these pipes were then connected to a vacuum pump via a trap and the
solution A was suctioned by reduced pressure into the polycarbonate
hollow fibers.
[0321] After the solution introduced into the polycarbonate hollow
fibers was removed to the trap, the one end of each of the
polycarbonate hollow fibers was removed from the containers
containing the solution A and, in that state, the vacuum pump was
operated. In this manner, air was suctioned into the hollow fibers,
resulting in solvent on the polycarbonate hollow fiber internal
walls being evaporated and PMMA monoacrylate being introduced onto
the hollow fiber internal walls 900 fibers were arrayed in 30 rows
by 30 layers by performing the fiber array step in accordance with
the second embodiment using the 30 fiber bonded fiber array flat
plates 120' in which 30 hollow fibers having PMMA monoacrylate
introduced onto the internal walls thereof that were obtained in
the above manner were bonded to concave rows 121, and using the 30
fiber array flat plates 120 to which fibers had not been bonded,
and using the same positioning member 130 as that used in Example
1.
[0322] Furthermore, in the task of arraying each layer, after the
sixth step had ended, a fiber bonding step was performed in which
the weight member 134 on the fixing jig 163 side and the fiber
array flat plate 120 beneath it are temporarily removed, and the
respective fibers are bonded to the concave rows 121 by coating the
same adhesive agent as that used in Example 1 between the hollow
fibers and the concave rows 121 where these hollow fibers are
arrayed. After the adhesive agent was smeared on in this manner,
the fiber array flat plate 120 and the weight member 134 were put
back in place and pressure was applied for several seconds at a
load of approximately 200N.
[0323] After the 30th layer of fibers was arrayed, then only if
another fiber array flat plate is to be placed on top thereof
(i.e., in the fourth step), a spacer 131 the same as that of
Example 1 in which no concave rows have been formed can be stacked
instead of the fiber array flat plate and used as a presser plate.
Namely, the spacer 131 that is stacked on the topmost layer is
fixed by screws to the base 133 of the positioning member 130. The
same tension imparting device 160 as in Example 1 was then used and
tension was imparted to each fiber such that a load of 15N acted
thereon.
(ii) Fiber Fixing Step
[0324] As is shown in FIG. 33, the hollow portion 193 of the
potting block 190 was filled with a curable resin solution.
[0325] Specifically, using the same potting block 190 as that used
in Example 1, the same Teflon (registered trademark) adhesive tape
as in Example 1 was stuck thereon. However, unlike Example 1,
instead of the filling aperture, a single aluminum plate (a) having
a circular resin pouring aperture with a diameter of 9.8 mm formed
therein was used. The resin pouring aperture was formed in the
center in the transverse direction of the aluminum plate (a) at a
position 12 mm from one of the short sides thereof. In addition,
the Teflon (registered trademark) adhesive tape was cut out in the
shape of the resin pouring aperture such that the Teflon
(registered trademark) adhesive tape did not block the resin
pouring aperture. These four pieces were then combined in the same
manner as in Example 1 so as to enclose the 30 rows by 30 layers of
polycarbonate hollow fibers to which organism related substance had
not been fixed that were arrayed in the above described (i) as is
shown in FIG. 33, and a 20 mm.times.20 mm.times.100 mm hollow
portion 193 was formed by the potting block 190. Note that the same
sealing member 195 as in Example 1 was interposed into the portion
of tight contact between the potting block 190 and the stacked
object 180a such that the supplied curable resin solution did not
leak from that portion. In addition, the stacked object 180a and
the potting block 190 were fastened together under pressure by the
fasteners 194 in the form of screws.
[0326] As is shown in FIG. 33, one end of a vinyl tube 198 having
an outer diameter of 10 mm and an inner diameter of 8 mm was pushed
into the resin pouring aperture formed in the aluminum plate (a)
and the other end thereof was connected to a funnel 199. The same
two-solution polyurethane resin as was used in Example 1 that had
been degassed by being stirred and mixed in a vacuum was then
poured into this funnel 199 so that the interior of the potting
block 190 was filled with resin.
[0327] In this state, after the resin was cured by being kept at
room temperature for 16 hours, the potting block 190 was
disassembled into four pieces, and a fiber array body made of
polycarbonate hollow fibers having the configuration shown in FIG.
35 (i.e., having 30 rows by 30 layers) was obtained in which gaps
between the polycarbonate hollow fibers were filled with
polyurethane resin, and whose cross-sectional dimensions were 20
mm.times.20 mm.times.length of 80 mm, and in which organism related
substance was fixed to the interior walls.
(2) Fixing of Organism Related Substance in A Hollow Fiber Array in
which Organism Related Substance has not been Fixed
[0328] Probe A and probe B that were synthesized in Reference
example 1 were added to the solvent B prepared in Reference example
3, and a probe A aqueous solution in which probe A was contained in
a concentration of 0.5 nmol/L and a probe B aqueous solution in
which probe B was contained in a concentration of 0.5 nmol/L were
prepared.
[0329] Next, all of the ends at one end of the polycarbonate hollow
fibers in portions of the obtained fiber array body that had not
been fixed by resin were bundled together, and the bundled portion
was bound using a rubber band. A portion slightly on the distal end
side of the bound portion was then cut. These cut ends were then
immersed in a cylindrical container having an internal diameter of
15 mm and a height of 30 mm and that was approximately 1/3.sup.rd
full of the same urethane resin solution that was used previously
to fix the fibers together. The urethane resin was then cured so
that the polycarbonate hollow fibers were sealed.
[0330] The other ends of the polycarbonate hollow fibers were
separated in alternating layers so that, out of all the layers, two
groups made up of 15 fibers by 30 layers were formed. The distal
ends of each bundle of 450 fibers was then inserted respectively
into containers containing the probe A aqueous solution and the
probe B aqueous solution.
[0331] Next, the fiber array bodies having the ends on one side
thereof sealed and having the ends on the other side thereof
inserted into containers containing the probe A aqueous solution or
the probe B aqueous solution were placed as they were inside a
thermal chamber and the interior of the chamber was held under
reduced pressure for 5 minutes. Thereafter, nitrogen gas was
gradually introduced into the chamber and the chamber was restored
to normal pressure. As a result, the probe A aqueous solution and
the probe B aqueous solution were drawn into the interior of the
hollow fibers. A polymerization reaction was then conducted using a
method in which the chamber that was full of nitrogen gas at normal
pressure was then heated for 3 hours at a set temperature of
70.degree. C., and the heating was then stopped and the chamber was
left at room temperature.
[0332] As a result, a polycarbonate hollow fiber array body was
obtained that held inside it a gel in which the probe A and probe
B, which are organism related substance, were fixed.
[0333] This fiber array body was then sliced into thin pieces
having a thickness of 0.5 mm and 140 organism related substance
fixed microarrays were obtained.
INDUSTRIAL APPLICABILITY
[0334] As has been described above, by using the fiber array device
of the present invention, it is possible to array fibers at a high
density accurately in an extremely short period of time. Moreover,
according to the present invention, it is also possible to prevent
errors when arraying fibers unlike when a conventional method is
used in which fibers are arrayed by being inserted into holes in a
jig.
[0335] Accordingly, according to the present invention, by
efficiently manufacturing fiber array bodies of fibers in which
organism related substance has been fixed, and then slicing these
into thin pieces in a direction intersecting the direction of the
fibers, it is possible to easily produce in mass organism related
substance fixed microarrays in which the type and quantity of a
specific organism related substance can be detected in a
sample.
[0336] Moreover, by using the fiber array jig of the present
invention, fibers can be efficiently arrayed three-dimensionally at
a high density and with a high degree of precision. Moreover, fiber
array bodies in which three-dimensionally arrayed fibers are fixed
by resin can be mass produced for industry.
[0337] Namely, if the fiber array jig of the present invention is
used, time and energy are not consumed by the task of inserting
fibers one by one through holes formed in a jig, as is the case
conventionally. Moreover, because it is not necessary to guide the
fibers being inserted to the holes using forceps or the like, the
problem of fibers that have already being inserted into adjacent
holes obstructing the operation of inserting fibers using forceps
does not arise. In addition, according to the present invention,
because the operation is not one of inserting the fibers into
holes, but of arraying them in the concave rows, even if the outer
diameter of the fibers is narrow and they have low rigidity, they
can be arrayed easily so that a greater degree of density in the
array of the fibers becomes possible.
[0338] Furthermore, when using the fiber array jig of the present
invention, the work involved in the fiber array step can be divided
so that, from this viewpoint as well, the productivity of the fiber
array body is improved.
[0339] Accordingly, by using the fiber array jig of the present
invention to manufacture fiber array bodies of fibers in which
organism related substance such as nucleic acids, proteins, and
polysaccharides and the like has been fixed, and then slicing these
into thin pieces in a direction intersecting the direction of the
fibers, it is possible to easily produce in mass organism related
substance fixed microarrays in which the type and quantity of a
specific organism related substance can be detected in a
sample.
[Array Table]
[0340] As per attached sheet [Array table free text] [0341] Array
number 1: Synthesized DNA [0342] Array number 2: Synthesized DNA
Sequence CWU 1
1
2 1 33 DNA Artificial Sequence Synthetic DNA 1 gcgatcgaaa
ccttgctgta cgagcgaggg ctc 33 2 32 DNA Artificial Sequence Synthetic
DNA 2 gatgaggtgg aggtcagggt ttgggacagc ag 32
* * * * *