U.S. patent application number 11/399409 was filed with the patent office on 2006-08-17 for beads alignment structure, production method thereof, and bead alignment method for capillary beads array.
This patent application is currently assigned to Hitachi Software Engineering Co., Ltd.. Invention is credited to Hiroshi Kishida, Osamu Kogi.
Application Number | 20060180734 11/399409 |
Document ID | / |
Family ID | 32906070 |
Filed Date | 2006-08-17 |
United States Patent
Application |
20060180734 |
Kind Code |
A1 |
Kogi; Osamu ; et
al. |
August 17, 2006 |
Beads alignment structure, production method thereof, and bead
alignment method for capillary beads array
Abstract
A method for producing a capillary bead array comprises the
steps of: dispensing beads into a liquid pool, outside a capillary,
having a depth of almost the same length as the particle diameter
of a bead; leveling the excessive beads by moving a leveling member
which is in contact with and relatively capable of be moved to the
liquid pool to remove excessive beads that the liquid pool cannot
contain; aligning the beads in the liquid pool one- or
two-dimensionally; bonding adjacent individual beads to each other;
producing a structure having the plurality of beads bonded and
aligned one- or two-dimensionally; removing the structure from the
liquid pool; and disposing the structure in the capillary formed of
soft resin, so that the beads comprising the plurality of beads
retaining the one- or two-dimensional alignment can be introduced
simultaneously into the capillary. This method reduces the time and
cost necessary for bead array production and retains the bead
alignment in the capillary, resulting in improved accuracy and
reliability in experiments using the capillary array.
Inventors: |
Kogi; Osamu; (Tokyo, JP)
; Kishida; Hiroshi; (Tokyo, JP) |
Correspondence
Address: |
REED SMITH LLP
Suite 1400
3110 Fairview Park Drive
Falls Church
VA
22042
US
|
Assignee: |
Hitachi Software Engineering Co.,
Ltd.
|
Family ID: |
32906070 |
Appl. No.: |
11/399409 |
Filed: |
April 7, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10765075 |
Jan 28, 2004 |
7052570 |
|
|
11399409 |
Apr 7, 2006 |
|
|
|
Current U.S.
Class: |
249/117 |
Current CPC
Class: |
B01J 2219/00659
20130101; B01J 2219/00585 20130101; B01L 3/502761 20130101; B01J
2219/00722 20130101; B01L 3/502707 20130101; B01J 2219/00466
20130101; B01L 2200/0668 20130101; C40B 40/06 20130101; B01J
2219/00657 20130101; Y10T 428/2982 20150115; B01J 2219/00648
20130101; B82Y 30/00 20130101; B01J 2219/00707 20130101; B01L
3/502753 20130101; B01J 19/0046 20130101; B01J 2219/005 20130101;
B01J 2219/00711 20130101; B01J 2219/00596 20130101 |
Class at
Publication: |
249/117 |
International
Class: |
B29C 33/00 20060101
B29C033/00 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 18, 2003 |
JP |
2003-113579 |
Claims
1. A bead alignment structure wherein a plurality of beads are
aligned one- or two-dimensionally and the beads are bonded to and
integrated with each other while retaining the alignment.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a Divisional application of U.S.
application Ser. No. 10/765,075 filed Jan. 28, 2004. Priority is
claimed based on U.S. application Ser. No. 10/765,075 filed Jan.
28, 2004, which claims the priority date of Japanese Patent
Application No. 2003-113579 filed Apr. 18, 2003, all of which is
incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Technical Field
[0003] The present invention relates to a method for aligning
particulate (granular) beads, and more particularly to a bead
alignment method for a capillary bead array having beads aligned in
a capillary formed on soft resin.
[0004] 2. Background Art
[0005] JP Patent Publication (Kokai) No. 2000-346842 A is mentioned
as prior art concerning a bead alignment method of a capillary bead
array. The patent document 1 discloses a technology to introduce
beads one by one into a capillary. This prior art is a method for
producing a probe array, wherein probe-immobilized fine particles
are aligned in a capillary or an optical cell in an order
determined in accordance with the type of probe. The method
comprises the steps of: retaining the fine particles in a narrow
introducing tube; releasing the fine particles one by one under
control with a solution into a flowing solution; and introducing
them into the capillary to align and retain the fine particles with
various probes immobilized thereon in the determined order. The
document 1 suggests that the beads introduced into the capillary
one by one remain aligned in the capillary.
[0006] In addition, JP Patent Publication (Kokai) No. 4-354532 A
(1992) discloses the invention wherein different microparticles or
different groups of microparticles are irradiated with a plurality
of laser beams, and trapped and manipulated with the purpose of
controlling the microparticles in a non-contact manner. However,
the invention of the document 2 relates to a micro-manipulation
technique of combining individual beads with each other, where such
technique only involves handling 2 to several microparticles at
most with forceps. In this way, the technique disclosed in the
patent document 2 requires complicated operations and lacks in
practicality. Therefore, there has been a demand for a technique to
align an extremely large number of beads one- or two-dimensionally
for the use of the beads in a capillary.
[0007] According to the existing method of the patent document 1 to
introduce beads one by one into a capillary, it takes a
progressively longer time to produce a bead array as the number of
beads to be introduced increases. The time length to produce a bead
array is directly linked to production cost thereof. Further, since
the bead alignment retention of the existing techniques relies on
capillary shape and size, there is a risk that the bead alignment
may become disordered in the capillary. The bead alignment
retention has a large impact on the accuracy or reliability of
experiments using capillary bead arrays.
SUMMARY OF THE INVENTION
[0008] It is therefore an object of the present invention to
enhance the accuracy and reliability of experiments using a
capillary bead array by retaining bead alignment in a capillary as
well as to reduce the time and cost necessary for bead array
production.
[0009] A first aspect of the present invention is a bead alignment
structure wherein a plurality of beads are aligned one- or
two-dimensionally and the beads are bonded to each other so as to
be integrated while retaining the alignment.
[0010] The bead used herein is a spherical object made of plastic
or glass and having a particle size of 0.1 .mu.m to 1 mm, and
preferably 1 .mu.m to 110 .mu.m. Specifically, beads such as
polystyrene beads, polypropylene beads and magnetic beads are used
to read fluorescent emissions or the like by the use of a flow
cytometer.
[0011] The bead alignment structure of the present invention is
characterized that beads are bonded to each other and integrated.
Thus, a large number of beads, such as from tens of to tens of
thousands of beads, can be integrated, and this is extremely
preferable for biochemical or immunological tests using beads.
[0012] The application of the bead alignment structure according to
the present invention is not limited, and it can be used as a bead
array for spotting DNAs. In addition, the bead alignment structure
may be installed inside various measurement apparatuses.
[0013] A second aspect of the present invention is a method for
producing the above integrated bead alignment structure. The method
comprises the steps of: aligning a plurality of beads one- or
two-dimensionally outside a capillary; and bonding the plurality of
beads while the bead alignment is retained.
[0014] According to the method of the present invention for
producing the integrated bead alignment structure, a plurality of
beads can be aligned one- or two-dimensionally in a predetermined
and desired order. Another bead alignment method comprises the
steps of: dispensing a plurality of beads into a liquid pool which
has a depth that is almost the same length as the particle diameter
of a bead and is disposed outside a capillary; removing excessive
beads that the liquid pool cannot contain by leveling the excessive
beads by moving a leveling member such as a plate-shape object
which is in contact with and relatively capable of being moved to
the liquid pool; filling the beads in the liquid pool one- or
two-dimensionally; and aligning the beads one- or
two-dimensionally.
[0015] Further, in a method for producing the integrated bead
alignment structure of the present invention comprises, it is
preferable:
[0016] to add dropwise or spray a solution containing a
photo-polymerization compound and a photo-polymerization initiator
to a liquid pool having the plurality of beads aligned one- or
two-dimensionally and to irradiate contact points of individual
adjacent beads with exciting light so as to photo-polymerize the
photo-polymerization compound; or
[0017] to add dropwise or spray a solution containing a
polymerization compound and a polymerization initiator to the
liquid pool having the plurality of beads aligned one- or
two-dimensionally and to heat the liquid pool so as to polymerize
the polymerization compound. Adjacent beads are thereby bonded and
a bead alignment structure having a plurality of beads aligned one-
or two-dimensionally is produced. Alternatively, when the plurality
of beads are made of plastic, an integrated bead alignment
structure having a plurality of beads aligned one- or
two-dimensionally can be produced by radiating laser light to the
vicinity of contact points of individual adjacent beads in the
liquid pool having the plurality of beads aligned one- or
two-dimensionally to temporarily melt the vicinity of the contact
points, thereby bonding adjacent beads to each other.
[0018] Although the integrated bead alignment structure of the
present invention has a plurality of beads aligned one- or
two-dimensionally, it can be easily made to be a structure in which
the beads are aligned three-dimensionally by stacking one bead
alignment structure upon another.
[0019] A third aspect of the present invention is a method for
aligning the above integrated bead alignment structure in a
capillary bead array having particulate beads aligned in a
capillary formed of soft resin. The method comprises aligning a
plurality of beads one- or two-dimensionally outside the capillary,
producing a bead alignment structure having the plurality of beads
bonded and integrated while the bead alignment is retained,
disposing the bead alignment structure in the capillary, and
introducing the beads comprising the plurality of beads retaining
one- or two-dimensional alignment into the capillary at the same
time.
[0020] According to the bead alignment method for a capillary bead
array of the present invention, it is possible to align a plurality
of beads one- or two-dimensionally in a predetermined and desired
order. Another alignment method comprises the steps of: dispensing
a plurality of beads in a liquid pool which has a depth that is
almost the same length as the particle diameter of a bead and is
placed outside a capillary; removing excessive beads that the
liquid pool cannot contain by leveling the excessive beads by
moving a leveling member such as a plate-shape object which is in
contact with and relatively capable of being moved to the liquid
pool; filling the beads in the liquid pool one- or
two-dimensionally; and aligning the beads one- or
two-dimensionally.
[0021] Additionally, in a method of the present invention for
aligning beads of a capillary bead array, it is preferable:
[0022] to add dropwise or spray a solution containing a
photo-polymerization compound and a photo-polymerization initiator
to a liquid pool having a plurality of beads aligned one- or
two-dimensionally and to irradiate contact points of individual
adjacent beads with exciting light so as to photo-polymerize the
photo-polymerization compound; or
[0023] to add dropwise or spray a solution containing a
polymerization compound and a polymerization initiator to a liquid
pool having a plurality of beads aligned one- or two-dimensionally
and to heat the liquid pool so as to polymerize the polymerization
compound,
[0024] thereby bonding adjacent beads to each other, so that a bead
alignment structure comprising a plurality of beads retaining a
one- or two-dimensional alignment is produced. Alternatively, when
the plurality of beads are made of plastic, a bead alignment
structure having a plurality of beads retaining a one- or
two-dimensional alignment can be produced by radiating laser light
to the vicinity of contact points of individual beads in the liquid
pool having the plurality of beads aligned one- or
two-dimensionally to temporarily melt the vicinity of the contact
points, thereby bonding adjacent beads to each other.
[0025] Furthermore, in a bead alignment method of a capillary bead
array of the present invention, it is preferable to introduce a
plurality of beads retaining a one- or two-dimensional alignment
into the capillary at the same time by taking out the bead
alignment structure having a plurality of beads retaining a one- or
two-dimensional alignment from the liquid pool and disposing it in
the capillary.
[0026] The above aspects of the present invention will be explained
more specifically. Initially, the plurality of beads are dispensed
into a liquid pool outside the capillary having a depth that is
almost the same length as the particle diameter of a bead, and
excessive beads that the liquid pool cannot contain are removed by
leveling the excessive beads by moving a leveling member which is
in contact with and relatively capable of being moved to the liquid
pool, thereby aligning the beads one- or two-dimensionally in the
liquid pool. A solution containing a photo-polymerization compound
and a photo-polymerization initiator are added dropwise or sprayed
to the liquid pool having the plurality of beads aligned one- or
two-dimensionally and exciting light is radiated to contact points
of adjacent beads, polymerizing the photo-polymerization compound
and allowing adjacent beads to be bonded. Alternatively, a solution
containing a polymerization compound and a polymerization initiator
is added dropwise or sprayed to the liquid pool having the
plurality of beads aligned one- or two-dimensionally and the liquid
pool is heated, polymerizing the polymerization compound and
allowing adjacent beads to be bonded. In this way, a structure
having a plurality of beads bonded to each other and aligned one-
or two-dimensionally is produced. The structure is removed from the
liquid pool and disposed in a capillary formed of soft resin. All
of the beads comprising the plurality of beads retaining a one- or
two-dimensional alignment can thereby be introduced into the
capillary at the same time. Furthermore, the bonding of the
plurality of beads aligned one- or two-dimensionally can eliminate
the risk of a disordered bead alignment and provide a method for
retaining the bead alignment without depending on the shape or the
size of a capillary.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1 shows an embodiment for aligning particulate beads
one- or two-dimensionally according to the present invention.
[0028] FIG. 2 shows an embodiment for producing a bead structure of
the present invention by bonding the plurality of beads aligned
one- or two-dimensionally.
[0029] FIG. 3 shows an embodiment for disposing in a capillary the
structure of the present invention comprising the plurality of
beads bonded to each other while the in one- or two-dimensional
alignment is retained.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0030] FIG. 1 is a schematic view showing an embodiment of the
present invention for aligning particulate beads one- or
two-dimensionally. A plurality of beads 101 are dispensed into a
liquid pool 102 having a depth of substantially the same magnitude
as the particle size of a bead 101 using a dispenser 103 (FIG.
1(a)). A leveling member 104 that is in contact with and relatively
capable of being moved to the liquid pool 102 is moved for leveling
beads 105, and excessive beads 106 that the liquid pool 102 cannot
contain are removed, so that beads 107 are aligned one- or
two-dimensionally in the liquid pool (FIG. 1(b) to (d)).
[0031] For convenience of explanation, FIG. 1 shows an integrated
bead alignment structure having a T-shape, but the bead alignment
structure of the present invention is not limited thereto. Any
shape having the plurality of beads aligned one- or
two-dimensionally can be used, for example, a one-dimensional
linear shape or a two-dimensional n.times.m rectangle.
[0032] FIG. 2 is a schematic view showing a method of the present
invention for producing a structure comprising a plurality of beads
bonded to each other and aligned one- or two-dimensionally. A
solution 203 containing a photo-polymerization compound and a
photo-polymerization initiator is added dropwise by a dispenser 204
to the liquid pool 202 having the plurality of beads 201 aligned
one- or two-dimensionally (FIG. 2(a)). An exciting light 207 from
an excitation light source 206 is radiated to a contact point 205
of adjacent beads through a lens 208 to allow the
photo-polymerization compound present on the bead contact point 205
irradiated with the exciting light 207 to be photo-polymerized,
thereby bonding adjacent beads 201 to each other (FIG. 2 (b)). The
integrated bead structure 209 is removed from the liquid pool 202
(FIG. 2 (c)). The liquid pool 202 or lens 208 is manipulated one-
or two-dimensionally to radiate the exciting light 207 to the
contact points 205 of all the beads 201 to be bonded. The structure
209 having a plurality of beads bonded to each other while a one-
or two-dimensional alignment is retained can be thereby
produced.
[0033] FIG. 3 is a schematic view showing a system wherein the
structure of the present invention comprising a plurality of beads
bonded to each other while a one- or two-dimensional alignment is
retained is placed in a capillary formed of soft resin. The
structure 301 having a plurality of beads bonded and aligned one-
or two-dimensionally is removed from the liquid pool 302 and placed
in the capillary 303 formed of soft resin. The beads comprising the
plurality of beads retaining one- or two-dimensional alignment can
be thereby simultaneously introduced into the capillary 303.
EFFECT OF THE INVENTION
[0034] According to the present invention, a structure wherein a
plurality of beads are bonded to each other while retaining a one-
or two-dimensional alignment can be easily and unfailingly
produced. In addition, the arrangement of the structure in a
capillary formed of soft resin or the like enables the beads
comprising the plurality of beads retaining the one- or
two-dimensional alignment to be easily and unfailingly introduced
simultaneously to the capillary. Further, the bonding of the
plurality of beads aligned one- or two-dimensionally can eliminate
the risk of the bead alignment becoming disordered and allow the
bead alignment to be retained without depending on the shape or the
size of the capillary, thereby reducing the cost of biochemical or
immunological examinations using beads and enabling a large
improvement of their accuracy.
* * * * *