U.S. patent application number 17/563680 was filed with the patent office on 2022-04-21 for microchip and particulate analyzing device.
The applicant listed for this patent is Sony Corporation. Invention is credited to Shoji AKIYAMA, Tatsumi ITO, Masaya KAKUTA, Takeshi YAMASAKI.
Application Number | 20220118444 17/563680 |
Document ID | / |
Family ID | 1000006056148 |
Filed Date | 2022-04-21 |
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United States Patent
Application |
20220118444 |
Kind Code |
A1 |
ITO; Tatsumi ; et
al. |
April 21, 2022 |
MICROCHIP AND PARTICULATE ANALYZING DEVICE
Abstract
A microchip is provided, which includes a substrate including a
fluid channel structure. The fluid channel structure includes a
first fluid introduction channel and a second fluid introduction
channel configured to meet so as to allow merging of a first fluid
introduced from the first fluid introduction channel and a second
fluid introduced from the second fluid introduction channel. A
tapered portion is configured to be positioned after merging the
first fluid and the second fluid so as to suppress a spiral flow
field generated after the merging.
Inventors: |
ITO; Tatsumi; (Kanagawa,
JP) ; AKIYAMA; Shoji; (Kanagawa, JP) ; KAKUTA;
Masaya; (Tokyo, JP) ; YAMASAKI; Takeshi;
(Kanagawa, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Sony Corporation |
Tokyo |
|
JP |
|
|
Family ID: |
1000006056148 |
Appl. No.: |
17/563680 |
Filed: |
December 28, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16927305 |
Jul 13, 2020 |
11229907 |
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17563680 |
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14879639 |
Oct 9, 2015 |
10744501 |
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16927305 |
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13580912 |
Aug 23, 2012 |
9176042 |
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PCT/JP2011/000902 |
Feb 18, 2011 |
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14879639 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 2200/10 20130101;
B01L 2300/0867 20130101; G01N 15/1056 20130101; B01L 3/502707
20130101; G01N 1/28 20130101; B01L 2200/12 20130101; G01N 15/1404
20130101; B01L 2300/0887 20130101; G01N 15/1484 20130101; G01N
2015/1413 20130101; B01L 3/502776 20130101 |
International
Class: |
B01L 3/00 20060101
B01L003/00; G01N 15/10 20060101 G01N015/10; G01N 15/14 20060101
G01N015/14; G01N 1/28 20060101 G01N001/28 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 1, 2010 |
JP |
2010-043968 |
Claims
1. A microfluidic chip for use with a particulate analyzing device,
the microfluidic chip comprising: a substrate; and a fluid channel
formed in the substrate, the fluid channel including: a supply port
configured to receive a sample liquid flow; and a merge channel
configured to convert the sample liquid flow into a sheath liquid
laminar flow, the merge channel having a first fluid converting
structure, a second fluid converting structure, and a third fluid
converting structure, to convert the sample liquid flow into the
sheath liquid laminar flow by introducing sheath liquid into the
fluid channel or changing a cross section area, wherein the first,
second, and third fluid converting structures are provided at
different longitudinal locations along the fluid channel, a first
surface portion of the fluid channel lies in a first plane upstream
of the second and third fluid converting structures, a second
surface portion of the fluid channel lies in a second plane
vertically above the first plane downstream of the second and third
fluid converting structures, and the first fluid converting
structure having a tapered portion narrowing the sample liquid flow
in a first direction, the second fluid converting structure having
a first portion narrowing the sample liquid flow in a second
direction, and the third fluid converting structure having a second
portion narrowing the sample liquid flow in the second direction,
and the first direction is orthogonal to the second direction.
2. The microfluidic chip of claim 1, further comprising a detection
portion downstream of the first, second, and third fluid converting
structures.
3. The microfluidic chip of claim 1, wherein the first fluid
converting structure is configured to introduce sheath liquid into
the fluid channel symmetrically with respect to a centerline of the
sample liquid flow.
4. The microfluidic chip of claim 1, wherein the first fluid
converting structure is configured to convert the sample liquid
flow in at least a lateral direction.
5. The microfluidic chip of claim 1, wherein the second fluid
converting structure is configured to convert the sample liquid
flow in at least a vertical direction.
6. The microfluidic chip of claim 1, wherein the third fluid
converting structure is configured to convert the sample liquid
flow in at least a vertical direction.
7. The microfluidic chip of claim 1, wherein the sample liquid flow
and the sheath liquid associated with the first fluid converting
structure enter the merge channel in a center line.
8. The microfluidic chip of claim 1, wherein the merge channel has
a varying width upstream of the second and third fluid converting
structures; and wherein the fluid channel has a constant width
between the second fluid converting structure and third fluid
converting structure.
9. The microfluidic chip of claim 8, wherein the fluid channel has
a constant width between a detection portion and the second and
third fluid converting structures.
10. The microfluidic chip of claim 1, wherein within the merge
channel the fluid channel transitions from a first cross section
shape to a second cross section shape different from the first
cross section shape.
11. The microfluidic chip of claim 1, wherein a first surface of
the fluid channel lies in a third plane upstream of the first and
second fluid converting structures, and a second surface of the
fluid channel lies in a fourth plane vertically below the third
plane downstream of the first and second fluid converting
structures.
12. The microfluidic chip of claim 1, wherein the first portion
includes a tapered portion.
13. The microfluidic chip of claim 1, wherein the second portion
includes a contracted portion.
14. The microfluidic chip of claim 1, wherein the merge channel
includes a focusing region.
15. A particulate analyzing device comprising: a detector
configured to detect particulates in a sample liquid flow in a
fluid channel formed in a substrate on a microfluidic chip, the
fluid channel including: a supply port configured to receive the
sample liquid flow; and a merge channel configured to convert the
sample liquid flow into a sheath liquid laminar flow, the merge
channel having a first fluid converting structure, a second fluid
converting structure, and a third fluid converting structure, to
convert the sample liquid flow into the sheath liquid laminar flow
by introducing sheath liquid into the fluid channel or changing a
cross section area, wherein the first, second, and third fluid
converting structures are provided at different longitudinal
locations along the fluid channel, a first surface portion of the
fluid channel lies in a first plane upstream of the second and
third fluid converting structures, a second surface portion of the
fluid channel lies in a second plane vertically above the first
plane downstream of the second and third fluid converting
structures, and the first fluid converting structure is a tapered
portion narrowing the sample liquid flow in a first direction, the
second fluid converting structure is a first portion narrowing the
sample liquid flow in a second direction, and the third fluid
converting structure is a second portion narrowing the sample
liquid flow in the second direction, and the first direction is
orthogonal to the second direction.
16. The particulate analyzing device of claim 15, further
comprising: a detection portion in the microfluidic chip downstream
of the first, second, and third fluid converting structures.
17. The particulate analyzing device of claim 15, wherein the first
fluid converting structure is configured to introduce sheath liquid
into the fluid channel symmetrically with respect to a centerline
of the sample liquid flow.
18. The particulate analyzing device of claim 15, wherein the first
fluid converting structure is configured to convert the sample
liquid flow in at least a lateral direction.
19. The particulate analyzing device of claim 15, wherein the
second fluid converting structure is configured to convert the
sample liquid flow in at least a vertical direction.
20. The particulate analyzing device of claim 15, wherein the third
fluid converting structure is configured to convert the sample
liquid flow in at least a vertical direction.
21. The particulate analyzing device of claim 15, wherein the
sample liquid flow and the sheath liquid associated with the first
fluid converting structure enter the merge channel in a center
line.
22. The particulate analyzing device of claim 15, wherein the merge
channel has a varying width upstream of the second and third fluid
converting structures; and wherein the fluid channel has a constant
width between the second fluid converting structure and third fluid
converting structure.
23. The particulate analyzing device of claim 22, wherein the fluid
channel has a constant width between a detection portion and the
second and third fluid converting structures.
24. The particulate analyzing device of claim 15, wherein within
the merge channel the fluid channel transitions from a first cross
section shape to a second cross section shape different from the
first cross section shape.
25. The particulate analyzing device of claim 15, wherein a first
surface of the fluid channel lies in a third plane upstream of the
first and second fluid converting structures, and a second surface
of the fluid channel lies in a fourth plane vertically below the
third plane downstream of the first and second fluid converting
structures.
26. The particulate analyzing device of claim 15, wherein the
sample liquid flow is narrowed such that the particulates are
arranged in a row downstream of the second and third fluid
converting structures, and the detector is configured to detect the
particulates one by one.
27. The particulate analyzing device of claim 15, wherein the
detector is included in at least one of an optical detection
system, an electrical detection system, or a magnetic detection
system.
28. The particulate analyzing device of claim 15, further
comprising an optical detection system, which includes the
detector, a laser beam source, an irradiation section including a
condenser lens configured to condense the laser beam and irradiate
the particulates, a dichroic mirror, and a bandpass filter.
29. The particulate analyzing device of claim 15, wherein the
detector comprises a pick-up element which is at least one of a
photo multiplier tube, a CCD or a CMOS device.
30. A system comprising: a particulate analyzing device; and a
microfluidic chip, wherein the microfluidic chip comprises: a
substrate; and a fluid channel formed in the substrate, the fluid
channel including: a supply port configured to receive a sample
liquid flow; and a merge channel configured to convert the sample
liquid flow into a sheath liquid laminar flow, the merge channel
having a first fluid converting structure, a second fluid
converting structure, and a third fluid converting structure, to
convert the sample liquid flow into the sheath liquid laminar flow
by introducing sheath liquid into the fluid channel or changing a
cross section area, wherein the first, second, and third fluid
converting structures are provided at different longitudinal
locations along the fluid channel, a first surface portion of the
fluid channel lies in a first plane upstream of the second and
third fluid converting structures, a second surface portion of the
fluid channel lies in a second plane vertically above the first
plane downstream of the second and third fluid converting
structures, and the first fluid converting structure having a
tapered portion narrowing the sample liquid flow in a first
direction, the second fluid converting structure having a first
portion narrowing the sample liquid flow in a second direction, and
the third fluid converting structure having a second portion
narrowing the sample liquid flow in the second direction, and the
first direction is orthogonal to the second direction.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S.
application Ser. No. 16/927,305, filed on Jul. 13, 2020, which is a
continuation of U.S. application Ser. No. 14/879,639, filed on Oct.
9, 2015, which is a continuation of U.S. application Ser. No.
13/580,912, filed on Aug. 23, 2012, which is a national stage of
International Application No. PCT/JP2011/000902 filed on Feb. 18,
2011, which claims priority to Japanese Patent Application No.
2010-043968 filed on Mar. 1, 2010, the disclosures of each of which
are incorporated herein by reference.
TECHNICAL FIELD
[0002] The present invention relates to a microchip and a
particulate analyzing device. More particularly, the present
invention relates to a microchip or the like for optically,
electrically or magnetically analyzing the characteristics of
particulates such as cells or microbeads in channels.
BACKGROUND
[0003] In recent years, microchips have been developed in which an
area and/or a channel or channels for performing chemical and
biological analyses are provided by application of micro-machining
techniques used in the semiconductor industry. These microchips
have begun to be utilized for electrochemical detectors in liquid
chromatography, small electrochemical sensors in medical service
sites, and the like.
[0004] Analytical systems using such microchips are called
micro-TAS (micro-Total-Analysis System), lab-on-a-chip, bio chip or
the like, and is paid attention to as a technology by which
chemical and biological analyses can be enhanced in speed,
efficiency and level of integration or by which analyzing devices
can be reduced in size.
[0005] The micro-TAS, which enables analysis with a small amount of
sample and enables disposable use of microchips, is expected to be
applied particularly to biological analyses where precious trace
amounts of samples or a multiplicity of specimens are treated.
[0006] An application example of the micro-TAS is a particulate
analyzing technology in which characteristics of particulates such
as cells and microbeads are analyzed optically, electrically or
magnetically in channels arranged on microchips. In the particulate
analyzing technology, fractional collection of a population
satisfying a predetermined condition or conditions from among
particulates on the basis of analytical results of the particulates
is also conducted.
[0007] Patent Literature 1, Japanese Patent Laid-open No.
2003-107099, for example, discloses "a particulate fractionation
microchip having a channel for introducing particulate-containing
solution, and a sheath flow forming channel arranged on at least
one lateral side of the introducing channel." The particulate
fractionation microchip further has "a particulate measuring
section for measuring the particulates introduced, at least two
particulate fractionating channels disposed on the downstream side
of the particulate measuring section so as to perform fractional
collection of the particulates, and at least two electrodes
disposed in the vicinity of channel ports opening from the
particulate measuring section into the particulate fractionating
channels so as to control the moving direction of the
particulates."
[0008] The particulate fractionation microchip disclosed in Patent
Literature 1, typically, is so designed that fluid laminar flows
are formed by a "trifurcated channel" having a channel for
introducing a particulate-containing solution and two sheath flow
forming channels (see "FIG. 1" of the literature).
[0009] FIGS. 17A and 17B show a trifurcated channel structure
according to related art (FIG. 17A), and sample liquid laminar
flows formed by the channel structure (FIG. 17B). In the
trifurcated channel, a sample liquid laminar flow passing through a
channel 101 in the direction of solid-line arrow in FIG. 17A can be
sandwiched, from the left and right sides, by sheath liquid laminar
flows introduced through channels 102, 102 in the directions of
dotted-line arrows in the figure. By this, as shown in FIG. 17B,
the sample liquid laminar flow can be fed through the center of the
channel. Incidentally, in FIG. 17B, the sample liquid laminar flow
is depicted in solid lines, and the channel structure in dotted
lines.
[0010] According to the trifurcated channel shown in FIGS. 17A and
17B, the sample liquid laminar flow is sandwiched by the sheath
liquid laminar flows from the left and right sides, whereby with
respect to the sandwiching direction (the Y-axis direction in FIGS.
17A and 17B), the sample liquid laminar flow can be fed in the
state of being deflected to an arbitrary position in the channel.
With respect to the vertical direction (the Z-axis direction in
FIGS. 17A and 17B) of the channel, however, it has been very
difficult to control the sample liquid feeding position. In other
words, in the trifurcated channel according to related art, it has
only been possible to form the sample laminar flow that is oblong
in the Z-axis direction.
[0011] Therefore, the microchip having the trifurcated channel
according to related art has the problem that in the case where,
for example, a particulate-containing solution as a sample liquid
is made to flow through a channel and subjected to optical
analysis, there would be a dispersion of the feeding position of
the particulates in the vertical direction (depth direction) of the
channel. Therefore, there has been the problem that the flowing
speed of particulates differs depending on the feeding position of
the particulates, variation of detection signals increases, and the
accuracy of analysis is degraded.
[0012] Patent Literature 2, Japanese Examined Patent Publication
No. 7-119686, discloses a channel structure that introduces a
sample liquid into the center of a sheath liquid laminar flow from
an opening at the center of the channel through which the sheath
liquid laminar flow is fed to thereby feed the sample liquid
laminar flow being surrounded by the sheath liquid laminar flow
(see FIGS. 2 and 3 of the literature). The channel structure
enables the sample liquid to be introduced into the center of the
sheath liquid laminar flow, thereby eliminating the dispersion of
the feeding position of the particulates in the depth direction of
the channel, so that the high accuracy of analysis can be
obtained.
[0013] FIGS. 18A and 18B show a channel structure according to
related art applied for introducing a sample liquid to the center
of a sheath liquid laminar flow (FIG. 18A), and a sample liquid
laminar flow formed by the channel structure (FIG. 18B). In this
channel structure, the sheath liquid laminar flow is introduced
into each of channels 102 and 102 in the direction of arrow T in
FIG. 18A and fed to a channel 103. Then, the sample liquid fed to a
channel 101 in the direction of arrow S can be introduced from an
opening 104 to the center of the sheath liquid laminar flow fed
through the channel 103. The sample liquid laminar flow can be
thereby fed, being converged to the center of the channel 103, as
shown in FIG. 18B. In FIG. 18B, the sample liquid laminar flow is
depicted in solid lines, and the channel structure in dotted
lines.
[0014] On the other hand, in Patent Literature 2, it is pointed out
that, when introducing the sample liquid laminar flow into the
sheath liquid laminar flow in such a channel structure, turbulence
occurs in the sample liquid laminar flow, which raises the case
where the sample liquid laminar flow is not a flat and stable
laminar flow (see the rows 12 to 46 in the right column on page 4
of the literature). Note that "flat laminar flow" indicates a
laminar flow converted in the depth direction (the Z-axis
direction) of the channel in FIGS. 18A and 18B, and "non-flat
laminar flow" indicates a laminar flow dispersed and spread in the
depth direction of the channel.
[0015] In the above Patent Literature, it is proposed to provide
the opening of the channel through which the sample liquid laminar
flow is introduced with a pair of plate projections (see the
reference numeral 18 in FIG. 10 of the literature) or the like in
order to suppress the turbulence (wake) of the laminar flow at the
merging portion of the sample liquid laminar flow and the sheath
liquid laminar flows. The plate projections 18 extend from the
opening wall of the channel through which the sample liquid laminar
flow is introduced in the flowing direction of the sample liquid
laminar flow and guides the sample liquid flowing out from the
opening.
SUMMARY
[0016] With the plate projections 18 disclosed in the above Patent
Literature 2, it is possible to guide the sample liquid flowing out
from the opening and let the sample liquid flow through the channel
as a stable laminar flow converged in the depth direction of the
channel.
[0017] However, the channel structure is complicated when such a
guide structure is provided at the opening of the channel through
which the sample liquid laminar flow is introduced. Further, it is
necessary to laminate three or more substrate onto one another in
order to form such a channel structure on a microchip. Therefore,
high accuracy is needed for the formation of the channel structure
on each substrate and the lamination of the substrates, which
increases the manufacturing cost of the microchip.
[0018] In light of the foregoing, it is desirable to provide a
microchip capable of feeding a sample liquid laminar flow converged
to the center of a channel and easily manufacturable.
[0019] According to an embodiment of the present invention, there
is provided a microchip, which includes a substrate including a
fluid channel structure. The fluid channel structure includes a
first fluid introduction channel and a second fluid introduction
channel configured to meet so as to allow merging of a first fluid
introduced from the first fluid introduction channel and a second
fluid introduced from the second fluid introduction channel. A
tapered portion is configured to be positioned after merging the
first fluid and the second fluid so as to suppress a spiral flow
field generated after the merging.
[0020] According to another embodiment of the present invention,
there is provided a particulate analyzing device, which includes a
microchip including a substrate that includes a fluid channel
structure. The fluid channel structure includes a first fluid
introduction channel and a second fluid introduction channel
configured to meet so as to allow merging of a first fluid
introduced from the first fluid introduction channel and a second
fluid introduced from the second fluid introduction channel. A
tapered portion is configured to be positioned after merging the
first fluid and the second fluid so as to suppress a spiral flow
field generated after the merging.
[0021] According to yet another embodiment of the present
invention, there is provided a method of manufacturing a microchip.
A substrate including a fluid channel structure is provided. The
fluid channel structure includes a first fluid introduction channel
and a second fluid introduction channel configured to meet so as to
allow merging of a first fluid introduced from the first fluid
channel and a second fluid introduced from the second fluid
introduction channel. A tapered portion is configured to be
positioned after merging the first fluid and the second fluid from
the first and second fluid introduction channels to suppress a
spiral flow field generated after the merging.
[0022] It should be noted that the "particulates" in the present
embodiment widely include microscopic bioparticles such as cells,
microorganisms, liposome, etc. as well as synthetic particles such
as latex particles, gel particles, industrial particles, etc. The
microscopic bioparticles include chromosome, liposome, mitocondria,
organelle, etc. which constitute various cells. The cells here
include animal cells (blood corpuscle cells, etc.) and plant cells.
The microorganisms includes bacteria such as colibacillus, etc.,
viruses such as tobacco mosaic virus, etc., and fungi such as
yeast, etc. Further, the microscopic bioparticles may include also
microscopic biopolymers such as nucleic acid, proteins, and
complexes thereof. The industrial particles may be, for example,
organic or inorganic polymer materials, metals or the like. The
organic polymer materials include polystyrene,
stylene-vinylbenzene, and polymethyl methacrylate. The inorganic
polymer materials include glass, silica, and magnetic materials.
The metals include gold colloid and aluminum. The shape of these
particulates is usually spherical, but may be non-spherical.
Besides, the particulates are not particularly limited as to size,
mass or the like.
[0023] According to the embodiments of the present invention
described above, a microchip capable of feeding a sample liquid
laminar flow converged to the center of a channel and easy
manufacturability is provided.
BRIEF DESCRIPTION OF DRAWINGS
[0024] FIGS. 1A and 1B are schematic diagrams illustrating a
channel structure on a microchip according to a first embodiment of
the present invention, in which FIG. 1A shows a top view and
[0025] FIG. 1B shows a sectional view;
[0026] FIGS. 2A, 2B and 2C are schematic diagrams illustrating
sections of a merge channel 12 of the microchip according to the
first embodiment of the present invention, in which FIG. 2A shows
section P-P, FIG. 2B shows section Q-Q, and FIG. 2C shows section
R-R, respectively in FIGS. 1A and 1B;
[0027] FIG. 3 is a schematic diagram illustrating a structure of a
communicating port 111 of the microchip according to the first
embodiment of the present invention;
[0028] FIGS. 4A and 4B are schematic diagrams illustrating a
structure of the communicating port 111 of the microchip according
to the first embodiment of the present invention (FIG. 4A) and an
opening 104 of a channel structure according to related art shown
in FIGS. 18A and 18B (FIG. 4B);
[0029] FIGS. 5A, 5B and 5C are schematic diagrams illustrating
alternative examples of a tapered portion 122 of the microchip
according to the first embodiment of the present invention, in
which the upper part shows a top view and the lower part shows a
sectional view;
[0030] FIGS. 6A and 6B are schematic diagrams illustrating a
channel structure on a microchip according to a second embodiment
of the present invention, in which FIG. 6A shows a top view and
FIG. 6B shows a sectional view;
[0031] FIGS. 7A, 7B and 7C are schematic diagrams illustrating
sections of a merge channel 12 of the microchip according to the
second embodiment of the present invention, in which FIG. 7A shows
section P-P, FIG. 7B shows section Q-Q, and FIG. 7C shows section
R-R, respectively in FIGS. 6A and 6B;
[0032] FIGS. 8A, 8B, and 8C are schematic diagrams illustrating
alternative examples of a tapered portion 123 of the microchip
according to the second embodiment of the present invention, in
which the upper part shows a top view and the lower part shows a
sectional view;
[0033] FIGS. 9A and 9B are schematic diagrams illustrating taper
angles in a depth direction of a channel of the tapered portion 123
of the microchip according to the second embodiment of the present
invention, in which the upper part shows a top view and the lower
part shows a sectional view;
[0034] FIGS. 10A and 10B are schematic diagrams illustrating an
alternative example of a tapered portion 123 and a contracted
position 121 of the microchip according to the second embodiment of
the present invention, in which FIG. 10A shows a top view and FIG.
10B shows a sectional view;
[0035] FIGS. 11A and 11B are schematic diagrams illustrating a
channel structure on a microchip according to a third embodiment of
the present invention, in which FIG. 11A shows a top view and FIG.
11B shows a sectional view;
[0036] FIGS. 12A, 12B and 12C are schematic diagrams illustrating
sections of a merge channel 12 of the microchip according to the
third embodiment of the present invention, in which FIG. 12A shows
section P-P, FIG. 12B shows section Q-Q, and FIG. 12C shows section
R-R, respectively in FIGS. 11A and 11B;
[0037] FIG. 13 is a schematic diagram illustrating an alternative
example of tapered portions 122 and 123 of the microchip according
to the third embodiment of the present invention, in which the
upper part shows a top view and the lower part shows a sectional
view;
[0038] FIGS. 14A and 14B are schematic diagrams illustrating an
alternative example of a tapered portion 123 and a contracted
position 121 of the microchip according to the third embodiment of
the present invention, in which FIG. 14A shows a top view and FIG.
14B shows a sectional view;
[0039] FIGS. 15A and 15B are diagrams illustrating a manufacturing
method of a microchip according to an embodiment of the present
invention, which show top schematic diagrams of substrates
constituting a chip;
[0040] FIGS. 16A and 16B are schematic diagrams illustrating a
manufacturing method of a microchip according to an embodiment of
the present invention, in which FIG. 16B shows a section along P-P
in FIG. 16A;
[0041] FIGS. 17A and 17B are schematic diagrams illustrating a
trifurcated channel structure according to related art (FIG. 17A),
and sample liquid laminar flows formed by the channel structure
(FIG. 17B);
[0042] FIGS. 18A and 18B are schematic diagrams illustrating a
channel structure according to related art applied for introducing
a sample liquid to the center of sheath liquid laminar flows (FIG.
18A), and sample liquid laminar flows formed by the channel
structure (FIG. 18B).
[0043] FIGS. 19A and 19B are schematic diagrams illustrating the
channel structure according to related art shown in FIGS. 18A and
18B, in which FIG. 19A shows a top view and FIG. 19B shows a
sectional view;
[0044] FIGS. 20A, 20B and 20C are schematic diagrams illustrating a
fluid velocity vector field in the channel structure according to
related art shown in FIGS. 18A and 18B, in which FIG. 20A shows
section P-P, FIG. 20B shows section Q-Q, and FIG. 20C shows section
R-R, respectively in FIGS. 19A and 19B; and
[0045] FIG. 21 is a schematic diagram illustrating a fluid velocity
vector field in the channel structure according to related art
shown in FIGS. 18A and 18B.
DETAILED DESCRIPTION
[0046] Preferred embodiments for carrying out the present invention
will be described hereinafter with reference to the drawings. Note
that the embodiments described below are typical exemplary
embodiments of the present invention, and the invention is not to
be narrowly construed due to the embodiments.
[0047] 1. Fluid Velocity Vector Field in Channel Structure
According to Related Art
[0048] The channel structure according to related art which is
applied for introducing a sample liquid to the center of a sheath
liquid laminar flow, shown in FIGS. 18A and 18B, has the problem
that, when introducing the sample liquid laminar flow into the
sheath liquid laminar flow, turbulence occurs in the sample liquid
laminar flow, and the sample liquid laminar flow is not converted
to the center of the channel.
[0049] Specifically, referring to FIGS. 19A and 19B, in the case
where a sample liquid laminar flow S is introduced from an opening
104 to the center of sheath liquid laminar flows T respectively
introduced to channels 102 and 102 and flowing through a channel
103, the sample liquid laminar flow S is dispersed in the depth
direction of the channel (the Z-axis direction) in some cases. If
the sample liquid laminar flow S is not converted to the center of
the channel, the feeding position of the particulates contained in
the sample liquid laminar flow S is dispersed in the depth
direction of the channel, and therefore, the detection signal of
the particulates also varies, which causes degradation of the
accuracy of analysis.
[0050] The inventors of the present invention have conducted
numerical calculation of the fluid velocity vector field (flow
field) in the channel structure in order to find a factor of the
turbulence of the sample liquid laminar flow occurring in the
channel structure according to related art. As a result, they have
found that the spiral flow field generated after the merging of the
sample liquid laminar flow and the sheath liquid laminar flows
causes the turbulence of the sample liquid laminar flow.
[0051] The fluid velocity vector field in the channel structure
according to related art is described with reference to FIGS. 19A
and 19B and FIGS. 20A to 20C. FIGS. 20A to 20C are schematic
sectional diagrams of the channel structure according to related
art, in which FIG. 20A shows section P-P, FIG. 20B shows section
Q-Q, and FIG. 20C shows section R-R, respectively in FIGS. 19A and
19B.
[0052] When the sample liquid laminar flow S is introduced from the
opening 104 into the center of the sheath liquid laminar flow T fed
through the channel 103, a high velocity vector appears at the
center in the depth direction of the channel immediately after the
introduction (see the arrows in FIG. 20A). It is considered that
the high velocity vector occurs because the merged sample liquid
laminar flow S and sheath liquid laminar flows T are concentrated
on the center of the depth direction of the channel for flowing
faster.
[0053] Further, in the process that the flow fields from the
channel 101 and the channels 102 and 102 are merged into one flow
field, a high velocity vector occurring at the center in the depth
direction of the channel grows into the flow field that rotates in
the Z-axis positive or negative direction as shown in FIG. 20B, and
further grows into the spiral flow field as shown in FIG. 20C.
Then, it has been founded that the sample liquid laminar flow S is
stretched out in the Z-axis positive and negative direction and
dispersed in the depth direction of the channel. It has been also
found that the deformation of the sample liquid laminar flow S due
to the spiral flow field becomes more significant depending on the
flow rate of the sheath liquids fed from the channels 102 and
102.
[0054] Furthermore, the inventors of the present invention have
found, as a result of the numerical calculation of the fluid
velocity vector field (flow field), that a slow flow field
occurring near the opening for introducing the sample liquid
laminar flow into the center of the sheath liquid laminar flow
causes the turbulence of the sample liquid laminar flow.
[0055] FIG. 21 schematically illustrates a slow flow field
occurring in the vicinity of an opening 104 of the channel
structure according to related art, shown in FIGS. 18A and 18B,
which is applied for introducing the sample liquid to the center of
the sheath liquid laminar flow.
[0056] In the vicinity of the opening 104, a shear force occurs
between the sheath liquid laminar flows T and the sample liquid
laminar flow S due to the merging of the sheath liquids fed from
the channels 102 and 102 and the sample liquid flowing out from the
opening 104. It has been found that, by the shear force, a slow
velocity vector occurs in the vicinity of the opening 104, and an
unstable flow field with a stagnant flow is generated. Due to the
stagnant flow field, the sample liquid laminar flow S becomes
unstable and dispersed in the depth direction of the channel. It
has been also found that the deformation of the sample liquid
laminar flow S due to the stagnant flow field becomes more
significant as the flow rate of the sample liquid flowing out of
the opening 104 is lower.
[0057] 2. Microchip According to First Embodiment of Invention
[0058] A first feature of a microchip according to an embodiment of
the present invention is to provide a channel structure that
suppresses the above-described spiral flow field generated after
merging of the sample liquid laminar flow and the sheath liquid
laminar flows and thereby avoids the turbulence of the sample
liquid laminar flow. A second feature of a microchip according to
an embodiment of the present invention is to provide a channel
structure that suppresses the above-described stagnant flow field
generated in the vicinity of an opening for introducing the sample
liquid laminar flow to the center of the sheath liquid laminar flow
and thereby avoids the turbulence of the sample liquid laminar
flow.
[0059] FIGS. 1A and 1B are schematic diagrams illustrating a
channel structure formed on a microchip according to a first
embodiment of the present invention, in which FIG. 1A shows a top
view and FIG. 1B shows a sectional view.
[0060] In the figures, the reference numeral 11 indicates a first
introduction channel (which is referred to hereinafter as a sample
liquid introduction channel 11) through which a first fluid
(referred to hereinafter as a sample liquid) is introduced. The
reference numerals 21 and 22 indicate second introduction channels
(referred to hereinafter as sheath liquid introduction channels 21
and 22) which are arranged to sandwich the sample liquid
introduction channel 11 and merged with the sample liquid
introduction channel 11 from the both sides thereof, and through
which a second fluid (referred to hereinafter as a sheath liquid)
is introduced. Further, the reference numeral 12 indicates a merge
channel which is connected to the sample liquid introduction
channel 11 and the sheath liquid introduction channels 21 and 22
and through which the sample liquid and the sheath liquids fed from
the respective channels are merged and flow.
[0061] The sample liquid introduction channel 11 has, at the
merging portion with the sheath liquid introduction channels 21 and
22, a communicating port 111 for introducing the sample liquid into
the center of the merge channel 12 through which the sheath liquid
laminar flow T flows. The channel depth of the sample liquid
introduction channel 11 in the Z-axis direction is designed to be
smaller than the channel depth of the sheath liquid introduction
channels 21 and 22, and the communicating port 111 is disposed at
substantially the center position in the channel depth direction of
the sheath liquid introduction channels 21 and 22. Further, the
communicating port 111 is also disposed at substantially the center
position in the channel width direction (the Y-axis direction) of
the merge channel 12.
[0062] By introducing the sample liquid laminar flow S to the
center of the sheath liquid laminar flow T from the communicating
port 111, the sample liquid laminar flow S can be fed in the state
of being surrounded by the sheath liquid laminar flow T (see also
FIGS. 2A, 2B and 2C described next). Note that the position where
the communicating port 111 is placed is not limited to the center
position of the channel depth direction of the sheath liquid
introduction channels 21 and 22 and may be in its vicinity, as long
as it allows the sample liquid laminar flow S to be fed into the
merge channel 12 in the state of being surrounded by the sheath
liquid laminar flow T. Likewise, the position of the communicating
port 111 in the channel width direction of the merge channel 12 is
not limited to the center position and may be in its vicinity.
[0063] In the figures, the reference numeral 122 indicates a
tapered portion that functions to suppress the spiral flow field
generated after the merging of the sample liquid laminar flow and
the sheath liquid laminar flows illustrated in FIG. 20. The tapered
portion 122 is disposed in the merge channel 12 in close proximity
to the merging portion of the sample liquid introduction channel 11
with the sheath liquid introduction channels 21 and 22. The tapered
portion 122 is formed so that the channel width in the sandwiching
direction (the Y-axis direction) along which the sample liquid
introduction channel 11 is sandwiched by sheath liquid introduction
channels 21 and 22 is enlarged gradually along the feeding
direction.
[0064] The fluid velocity vector field in the merge channel 12 and
the function of the tapered portion 122 are described with
reference to FIGS. 1A and 1B and FIGS. 2A to 2C. FIGS. 2A, 2B and
2C are schematic sectional diagrams of the merge channel 12, in
which FIG. 2A shows section P-P, FIG. 2B shows section Q-Q, and
FIG. 2C shows section R-R, respectively in FIGS. 1A and 1B.
[0065] When the sample liquid laminar flow S is introduced from an
opening 111 into the center of the sheath liquid laminar flow T
flowing through the merge channel 12, a high velocity vector
appears at the center in the depth direction of the channel
immediately after the introduction (see the dotted-line arrows in
FIG. 2A). The high velocity vector occurs because the merged sample
liquid laminar flow S and sheath liquid laminar flows T are
concentrated on the center of the depth direction of the channel
for flowing faster as described earlier.
[0066] At the tapered portion 122, when the laminar flow width of
the merged sample liquid laminar flow S and sheath liquid laminar
flow T is enlarged in the Y-axis direction, a flow field (see the
solid-line arrows in FIG. 2B), which is in reverse direction to the
high velocity vector generated at the center in the depth direction
of the channel, is generated. By generating the reverse flow field,
the tapered portion 122 cancels out the flow field generated at the
center in the depth direction of the channel and thereby prevents
the flow field from growing into the spiral flow field. As a
result, the sample liquid laminar flow S is maintained in the state
of being converted to the center of the channel without being
stretched out in the Z-axis direction by the spiral flow field (see
FIGS. 2B and 2C).
[0067] In the figures, the reference numeral 121 indicates a
contracted portion that functions to narrow down the laminar flow
width of the merged sample liquid laminar flow S and sheath liquid
laminar flow T in the Y-axis direction and the Z-axis direction.
The contracted portion 121 is disposed on the downstream side of
the tapered portion 122. The contracted portion 121 is formed so
that the channel width is reduced gradually along the feeding
direction. Further, the contracted portion 121 is formed so that
the channel depth is also reduced gradually along the feeding
direction. Specifically, the channel wall of the contracted portion
121 is formed to be narrowed along the feeding direction in the
Y-axis and the Z-axis directions, and the contracted portion 121 is
formed so that the area of the vertical section with respect to the
feeding direction (the X-axis positive direction) decreases
gradually. With such a shape, the contracted portion 121 feeds the
liquids by narrowing down the laminar flow width of the merged
sample liquid laminar flow S and sheath liquid laminar flow T in
the Y-axis direction and the Z-axis direction.
[0068] FIG. 3 and FIGS. 4A and 4B are schematic diagrams
illustrating a structure of the communicating port 111. The channel
depth of the sample liquid introduction channel 11 in the Z-axis
direction is designed to be smaller than the channel depth of the
sheath liquid introduction channels 21 and 22, and the
communicating port 111 is placed at substantially the center
position of the channel depth direction of the sheath liquid
introduction channels 21 and 22 (see FIG. 3). Further, in order to
suppress the stagnant flow field generated in the vicinity, the
communicating port 111 opens in an area including channel walls 211
and 221 of the sheath liquid introduction channel 21 and the sheath
liquid introduction channel 22.
[0069] This is described specifically with reference to FIGS. 4A
and 4B. First, a structure of the opening 104 in the channel
structure according to related art (see FIGS. 18A and 18B) is
described with reference to FIG. 4B. In the channel structure
according to related art, by a shear force which occurs between the
sheath liquid laminar flows T and the sample liquid laminar flow S
due to the merging of the sheath liquids fed from the channels 102
and 102 and the sample liquid flowing out from the opening 104, an
unstable flow field with a stagnant flow (the diagonally shaded
area in FIG. 4B) is generated in the vicinity of the opening 104
(see also FIG. 21).
[0070] In this case, the sample liquid flows out to the stagnant,
unstable flow field from the opening 104. Consequently, the sample
liquid laminar flow S becomes unstable before coming into contact
with the fast-flowing sheath liquids fed from the channels 102 and
102 and dispersed in the depth direction of the channel.
[0071] On the other hand, because the communicating port 111 of the
microchip according to the embodiment opens in an area including
the channel walls 211 and 221 of the sheath liquid introduction
channel 21 and the sheath liquid introduction channel 22, the
sample liquid flowing out of the communicating port 111 comes into
direct contact with the fast-flowing sheath liquids fed through the
sheath liquid introduction channels 21 and 22. Consequently, the
sample liquid laminar flow S is accelerated by the sheath liquids
immediately after flowing out of the communicating port 111 and
thereby maintained in the stable state of being converted to the
center of the channel without being dispersed in the depth
direction.
[0072] Note that the shape of the communicating port 111 described
herein may be regarded as a shape that the side end of the
communicating port 111 of the sample liquid introduction channel 11
is cut out by the channel walls 211 and 221 of the sheath liquid
introduction channel 21 and the sheath liquid introduction channel
22. Because the shape of the communicating port 111 is made by the
cutout by the channel walls 211 and 221 of the sheath liquid
introduction channel 21 and the sheath liquid introduction channel
22, the channel width indicated by the symbol W in FIG. 4A is
designed to be smaller than the channel width after cutout
indicated by the symbol C.
[0073] 3. Alternative Example of Channel Structure of Microchip
According to First Embodiment
[0074] FIG. 1A illustrates the case where the tapered portion 122
is disposed in the merge channel 12 on the downstream side of the
communicating port 111, which is the merging portion of the sample
liquid introduction channel 11 with the sheath liquid introduction
channels 21 and 22. However, the position where the tapered portion
122 is disposed is not limited to the position shown in FIG. 1A, as
long as it is in close proximity to the merging portion of the
sample liquid introduction channel 11 with the sheath liquid
introduction channels 21 and 22.
[0075] FIGS. 5A, 5B and 5C show alternative examples of the tapered
portion 122, in which the upper part shows a top schematic view and
the lower part shows a sectional schematic view. As shown in FIG.
5A, for example, the tapered portion 122 may be placed so that the
point at which the channel width in the Y-axis direction begins to
increase is located on the upstream side of the communicating port
111. Further, as shown in FIG. 5B, the tapered portion 122 may be
placed so that the point at which the channel width in the Y-axis
direction begins to increase is located at the position coinciding
with the communicating port 111. Note that FIG. 5C shows the case
where the point at which the channel width in the Y-axis direction
begins to increase is located on the downstream side of the
communicating port 111 and the tapered portion 122 is placed on the
downstream side of the communicating port 111.
[0076] 4. Microchip According to Second Embodiment of Invention
[0077] FIGS. 6A and 6B are schematic diagrams illustrating a
channel structure on a microchip according to a second embodiment
of the present invention, in which FIG. 6A shows a top view and
FIG. 6B shows a sectional view.
[0078] In the figures, the reference numeral 11 indicates a sample
liquid introduction channel through which a sample liquid is
introduced. The reference numerals 21 and 22 indicate sheath liquid
introduction channels which are arranged to sandwich the sample
liquid introduction channel 11 and merged with the sample liquid
introduction channel 11 from the both sides thereof, and through a
sheath liquid is introduced. Further, the reference numeral 12
indicates a merge channel which is connected to the sample liquid
introduction channel 11 and the sheath liquid introduction channels
21 and 22 and through which the sample liquid and the sheath
liquids fed from the respective channels are merged and flow.
[0079] The sample liquid introduction channel 11 has, at the
merging portion with the sheath liquid introduction channels 21 and
22, a communicating port 111 for introducing the sample liquid into
the center of the merge channel 12 through which the sheath liquid
laminar flow T flows.
[0080] The channel depth of the sample liquid introduction channel
11 in the Z-axis direction is designed to be smaller than the
channel depth of the sheath liquid introduction channels 21 and 22,
and the communicating port 111 is disposed at substantially the
center position in the channel depth direction of the sheath liquid
introduction channels 21 and 22. Further, the communicating port
111 is also disposed at substantially the center position in the
channel width direction (the Y-axis direction) of the merge channel
12.
[0081] By introducing the sample liquid laminar flow S to the
center of the sheath liquid laminar flow T from the communicating
port 111, the sample liquid laminar flow S can be fed in the state
of being surrounded by the sheath liquid laminar flow T (see also
FIG. 7 described next). Note that the position where the
communicating port 111 is placed is not limited to the center
position of the channel depth direction of the sheath liquid
introduction channels 21 and 22 and may be in its vicinity, as long
as it allows the sample liquid laminar flow S to be fed into the
merge channel 12 in the state of being surrounded by the sheath
liquid laminar flow T. Likewise, the position of the communicating
port 111 in the channel width direction of the merge channel 12 is
not limited to the center position and may be in its vicinity.
[0082] In the figures, the reference numeral 123 indicates a
tapered portion that functions to suppress the spiral flow field
generated after the merging of the sample liquid laminar flow and
the sheath liquid laminar flows illustrated in FIG. 20. The tapered
portion 123 is disposed in the merge channel 12 in close proximity
to the merging portion of the sample liquid introduction channel 11
with the sheath liquid introduction channels 21 and 22. The tapered
portion 123 is formed so that the channel depth in the vertical
direction (the Z-axis direction) perpendicular to the plane (X-Y
plane) containing the sample liquid introduction channel 11 and the
sheath liquid introduction channels 21 and 22 is narrowed gradually
along the feeding direction.
[0083] The fluid velocity vector field in the merge channel 12 and
the function of the tapered portion 123 are described with
reference to FIGS. 6A and 6B and FIGS. 7A to 7C. FIGS. 7A, 7B and
7C are schematic sectional diagrams of the merge channel 12, in
which FIG. 7A shows section P-P, FIG. 7B shows section Q-Q, and
FIG. 7C shows section R-R, respectively in FIGS. 6A and 6B.
[0084] When the sample liquid laminar flow S is introduced from an
opening 111 into the center of the sheath liquid laminar flow T
flowing through the merge channel 12, a high velocity vector
appears at the center in the depth direction of the channel
immediately after the introduction (see the dotted-line arrows in
FIG. 7A). The high velocity vector occurs because the merged sample
liquid laminar flow S and sheath liquid laminar flows T are
concentrated on the center of the depth direction of the channel
for flowing faster as described earlier.
[0085] At the tapered portion 123, when the laminar flow width of
the merged sample liquid laminar flow S and sheath liquid laminar
flow T is narrowed in the Z-axis direction, a flow field (see the
solid-line arrows in FIG. 7B), which is in reverse direction to the
high velocity vector generated at the center in the depth direction
of the channel, is generated. By generating the reverse flow field,
the tapered portion 123 cancels out the flow field generated at the
center in the depth direction of the channel and thereby prevents
the flow field from growing into the spiral flow field. As a
result, the sample liquid laminar flow S is maintained in the state
of being converted to the center of the channel without being
stretched out in the Z-axis direction by the spiral flow field (see
FIGS. 7B and 7C).
[0086] In the figures, the reference numeral 121 indicates a
contracted portion that functions to narrow down the laminar flow
width of the merged sample liquid laminar flow S and sheath liquid
laminar flow T in the Y-axis direction and the Z-axis direction.
The structure and the action of the contracted portion 121 are the
same as those in the microchip according to the first embodiment
and not redundantly described. Further, the structure and the
action of the communicating port 111 are also the same as those in
the microchip according to the first embodiment.
[0087] 5. Alternative Example of Channel Structure of Microchip
According to Second Embodiment
[0088] FIG. 6B illustrates the case where the tapered portion 123
is disposed so that the point at which the channel depth in the
Z-axis direction begins to decrease coincides with the position of
the communicating port 111. However, the position where the tapered
portion 123 is disposed is not limited to the position shown in
FIG. 6B, as long as it is in close proximity to the merging portion
of the sample liquid introduction channel 11 with the sheath liquid
introduction channels 21 and 22.
[0089] FIGS. 8A, 8B and 8C show alternative examples of the tapered
portion 123, in which the upper part shows a top schematic view and
the lower part shows a sectional schematic view, of the tapered
portion 123. As shown in FIG. 8A, for example, the tapered portion
123 may be placed so that the point at which the channel depth in
the Z-axis direction begins to decrease is located on the upstream
side of the communicating port 111. Further, as shown in FIG. 8C,
the tapered portion 123 may be placed so that the point at which
the channel depth in the Z-axis direction begins to decrease is
located on the downstream side of the communicating port 111. Note
that FIG. 8B shows the case where the point at which the channel
depth in the Z-axis direction begins to decrease is located at the
position coinciding with the communicating port 111 as in the case
of FIGS. 6A and 6B.
[0090] A taper angle (see the symbol (theta)z in FIGS. 9A and 9B)
in the channel depth direction of the tapered portion 123 may be
set to any value as long as the function of the tapered portion 123
can be exerted. By setting the taper angle (theta)z to be larger
than the merging angle (see the symbol (theta)y in FIG. 9A) of the
sheath liquid introduction channels 21 and 22 with the sample
liquid introduction channel 11, the effect of suppressing the
generation of the spiral flow field can be enhanced. Further, in
the case where the channel width of the merge channel 12 is
designed to be reduced gradually along the feeding direction, by
setting the taper angle (theta)z to be larger than the draw angle
(see the symbol (theta)y in FIG. 9B) of the merge channel 12, the
sufficient effect of suppressing the spiral flow field can be
obtained.
[0091] Although the case where the tapered portion 123 and the
contracted portion 121 are formed discontinuously is illustrated in
FIGS. 6A and 6B, the tapered portion 123 and the contracted portion
121 may be formed continuously as illustrated in FIGS. 10A and
10B.
[0092] 6. Microchip According to Third Embodiment of Invention
[0093] FIGS. 11A and 11B are schematic diagrams illustrating a
channel structure on a microchip according to a third embodiment of
the present invention, in which FIG. 11A shows a top view and FIG.
11B shows a sectional view, respectively of the microchip.
[0094] In the figures, the reference numeral 11 indicates a sample
liquid introduction channel through which a sample liquid is
introduced. The reference numerals 21 and 22 indicate sheath liquid
introduction channels which are arranged to sandwich the sample
liquid introduction channel 11 and merged with the sample liquid
introduction channel 11 from the both sides thereof, and through a
sheath liquid is introduced. Further, the reference numeral 12
indicates a merge channel which is connected to the sample liquid
introduction channel 11 and the sheath liquid introduction channels
21 and 22 and through which the sample liquid and the sheath
liquids fed from the respective channels are merged and flow.
[0095] The sample liquid introduction channel 11 has, at the
merging portion with the sheath liquid introduction channels 21 and
22, a communicating port 111 for introducing the sample liquid into
the center of the merge channel 12 through which the sheath liquid
laminar flow T flows.
[0096] The channel depth of the sample liquid introduction channel
11 in the Z-axis direction is designed to be smaller than the
channel depth of the sheath liquid introduction channels 21 and 22,
and the communicating port 111 is disposed at substantially the
center position in the channel depth direction of the sheath liquid
introduction channels 21 and 22. Further, the communicating port
111 is also disposed at substantially the center position in the
channel width direction (the Y-axis direction) of the merge channel
12.
[0097] By introducing the sample liquid laminar flow S to the
center of the sheath liquid laminar flow T from the communicating
port 111, the sample liquid laminar flow S can be fed in the state
of being surrounded by the sheath liquid laminar flow T (see also
FIG. 12 described next). Note that the position where the
communicating port 111 is placed is not limited to the center
position of the channel depth direction of the sheath liquid
introduction channels 21 and 22 and may be in its vicinity, as long
as it allows the sample liquid laminar flow S to be fed into the
merge channel 12 in the state of being surrounded by the sheath
liquid laminar flow T. Likewise, the position of the communicating
port 111 in the channel width direction of the merge channel 12 is
not limited to the center position and may be in its vicinity.
[0098] In the figures, the reference numerals 122 and 123 indicate
tapered portions that function to suppress the spiral flow field
generated after the merging of the sample liquid laminar flow and
the sheath liquid laminar flows illustrated in FIG. 20. The tapered
portions 122 and 123 are disposed in the merge channel 12 in close
proximity to the merging portion of the sample liquid introduction
channel 11 with the sheath liquid introduction channels 21 and 22.
The tapered portion 122 is formed so that the channel width in the
sandwiching direction (the Y-axis direction) along which the sample
liquid introduction channel 11 is sandwiched by sheath liquid
introduction channels 21 and 22 is enlarged gradually along the
feeding direction. Further, the tapered portion 123 is formed so
that the channel depth in the vertical direction (the Z-axis
direction) perpendicular to the plane (X-Y plane) containing the
sample liquid introduction channel 11 and the sheath liquid
introduction channels 21 and 22 is narrowed gradually along the
feeding direction. In the microchip according to the embodiment,
the tapered portions 122 and 123 are formed in a partially overlap
area of the merge channel 12.
[0099] The fluid velocity vector field in the merge channel 12 and
the function of the tapered portions 122 and 123 are described with
reference to FIGS. 11A and 11B and FIGS. 12A to 12C. FIGS. 12A, 12B
and 12C are schematic sectional diagrams of the merge channel 12,
in which FIG. 12A shows section P-P, FIG. 12B shows section Q-Q,
and FIG. 12C shows section R-R, respectively in FIGS. 11A and
11B.
[0100] When the sample liquid laminar flow S is introduced from an
opening 111 into the center of the sheath liquid laminar flow T
flowing through the merge channel 12, a high velocity vector
appears at the center in the depth direction of the channel
immediately after the introduction (see the dotted-line arrows in
FIG. 12A). The high velocity vector occurs because the merged
sample liquid laminar flow S and sheath liquid laminar flows T are
concentrated on the center of the depth direction of the channel
for flowing faster as described earlier.
[0101] At the tapered portion 122, when the laminar flow width of
the merged sample liquid laminar flow S and sheath liquid laminar
flow T is enlarged in the Y-axis direction, and at the tapered
portion 123, when the laminar flow width of the merged sample
liquid laminar flow S and sheath liquid laminar flow T is narrowed
in the Z-axis direction, a flow field (see the solid-line arrows in
FIG. 12B), which is in reverse direction to the high velocity
vector generated at the center in the depth direction of the
channel, is generated. By generating the reverse flow field, the
tapered portions 122 and 123 cancel out the flow field generated at
the center in the depth direction of the channel and thereby
prevent the flow field from growing into the spiral flow field. As
a result, the sample liquid laminar flow S is maintained in the
state of being converted to the center of the channel without being
stretched out in the Z-axis direction by the spiral flow field (see
FIGS. 12B and 12C).
[0102] In the figures, the reference numeral 121 indicates a
contracted portion that functions to narrow down the laminar flow
width of the merged sample liquid laminar flow S and sheath liquid
laminar flow T in the Y-axis direction and the Z-axis direction.
The structure and the action of the contracted portion 121 are the
same as those in the microchip according to the first embodiment
and not redundantly described. Further, the structure and the
action of the communicating port 111 are also the same as those in
the microchip according to the first embodiment.
[0103] 7. Alternative Example of Channel Structure of Microchip
According to Third Embodiment
[0104] FIG. 11A illustrates the case where the tapered portion 122
is disposed in the merge channel 12 on the downstream side of the
communicating port 111, which is the merging portion of the sample
liquid introduction channel 11 with the sheath liquid introduction
channels 21 and 22. However, the position where the tapered portion
122 is disposed is not limited to the position shown in FIG. 11A,
as long as it is in close proximity to the merging portion of the
sample liquid introduction channel 11 with the sheath liquid
introduction channels 21 and 22.
[0105] Further, FIG. 11B illustrates the case where the tapered
portion 123 is disposed so that the point at which the channel
depth in the Z-axis direction begins to decrease coincides with the
position of the communicating port 111. However, the position where
the tapered portion 123 is disposed is not limited to the position
shown in FIG. 11B, as long as it is in close proximity to the
merging portion of the sample liquid introduction channel 11 with
the sheath liquid introduction channels 21 and 22.
[0106] Furthermore, FIGS. 11A and 11B illustrate the case where the
point of the tapered portion 123 at which the channel depth in the
Z-axis direction begins to decrease is disposed on the upstream
side of the point of the tapered portion 122 at which the channel
width in the Y-axis direction begins to increase. However, the
point at which the tapered portion 122 begins and the point at
which the tapered portion 123 begins may be different or the same.
Likewise, although FIGS. 11A and 11B illustrate the case where the
point of the tapered portion 122 at which the channel width in the
Y-axis direction ends to increase and the point of the tapered
portion 123 at which the channel depth in the Z-axis direction ends
to decrease are disposed on the same position, the point at which
the tapered portion 122 ends and the point at which the tapered
portion 123 ends may be different or the same.
[0107] FIG. 13 shows an alternative example of the tapered portions
122 and 123. In this alternative example, the positions of the
point of the tapered portion 122 at which the channel width in the
Y-axis direction begins to increase and the point of the tapered
portion 123 at which the channel depth in the Z-axis direction
begins to decrease both coincide with the communicating port 111.
Further, the positions of the point at which the tapered portion
122 ends and the point at which the tapered portion 123 ends also
coincide with each other.
[0108] Further, although the case where the tapered portion 123 and
the contracted portion 121 are formed discontinuously is
illustrated in FIGS. 11A and 11B, the tapered portion 123 and the
contracted portion 121 may be formed continuously as illustrated in
FIGS. 14A and 14B.
[0109] 8. Manufacturing of Microchip According to Invention
[0110] The material of the microchip according to the embodiment of
the present invention may be glass or various kinds of plastic (PP,
PC, COP, PDMS). In the case where the analysis using the microchip
is carried out optically, it is preferred to select a material
having light transmittance, with low autofluorescence, and with
small optical errors because of small wavelength dispersion.
[0111] In order to maintain the light transmittance of the
microchip, its surface is preferably coated with a so-called hard
coat layer which is used for an optical disc. If a stain such as
fingerprints is attached to the surface of the microchip,
particularly, the surface of an optical detector, the amount of
light transmission decreases to cause the degradation of accuracy
of optical analyses. By depositing the hard coat layer with high
transparency and stain resistance on the surface of the microchip,
the degradation of accuracy of analysis can be prevented.
[0112] The hard coat layer can be formed by use of one of the hard
coating agents which are used ordinarily, for example, a UV-curing
type hard coating agent admixed with a fingerprint stain-proofing
agent such as a fluoro or silicone stain-proofing agent. Japanese
Patent Laid-open No. 2003-157579 discloses an active energy ray
curable composition (P) as a hard-code agent which contains a
multifunctional compound (A) having at least two polymerizable
functional groups capable of being polymerized under active energy
rays, modified colloidal silica (B) whose average particle diameter
is 1 to 200 nm, and whose surface has been modified by a
mercaptosilane compound in which an organic group having a mercapto
group and a hydrolysable group or hydroxyl group are bonded to
silicon atom, and a photopolymerization initiator (C).
[0113] Forming of the sample liquid introduction channel 11, the
sheath liquid introduction channels 21 and 22, the merge channel 12
having the tapered portions 122 and 123 and the contracted portion
121 and the like arranged in the microchip can be carried out by
wet etching or dry etching of a glass-made substrate layer, or by
nanoimprint technique or injection molding or cutting of a
plastic-made substrate layer. Then, the two substrates on which the
sample liquid introduction channel 11 and the like is formed are
laminated onto each other, whereby the microchip can be fabricated.
The lamination of the substrates onto each other can be carried out
by appropriately using a known method, such as heat fusing,
adhesion with an adhesive, anodic bonding, bonding by use of a
pressure sensitive adhesive-coated sheet, plasma-activated bonding,
ultrasonic bonding, etc.
[0114] A manufacturing method of the microchip according to the
embodiment of the present invention is described hereinafter with
reference to FIGS. 15A and 15B and FIGS. 16A and 16B. FIGS. 15A and
15B show top schematic diagrams of substrates constituting the
microchip according to the embodiment of the present invention.
FIGS. 16A and 16B show sectional diagrams of the microchip
according to the embodiment of the present invention. FIG. 16B
shows section P-P in FIG. 16A.
[0115] First, part of the sheath liquid introduction channels 21
and 22 and part of the merge channel 12 are made on a substrate a
(see FIG. 15A). On the substrate a, a sample liquid supply port 3
for supplying a sample liquid to the sample liquid introduction
channel 11, a sheath liquid supply port 4 for supplying a sheath
liquid to the sheath liquid introduction channels 21 and 22, and an
discharge port for discharging the sample liquid and the sheath
liquid from the merge channel 12 are also made. Next, the sample
liquid introduction channel 11, part of the sheath liquid
introduction channels 21 and 22 and part of the merge channel 12
are made on a substrate b (see FIG. 15B).
[0116] Next, the substrate a and the substrate b are laminated onto
each other by thermocompression bonding or the like as shown in
FIGS. 16A and 16B, whereby the microchip can be fabricated. In this
step, the sheath liquid introduction channels 21 and 22 are created
at different depths on the substrates a and b so that the sample
liquid introduction channel 11 is located at substantially the
center in the channel depth direction of the sheath liquid
introduction channels 21 and 22.
[0117] As described above, the microchip according to the
embodiment of the present invention may be manufactured by
laminating the substrates a and b on which the sample liquid
introduction channel 11 and the like is made. Therefore,
differently from the microchip disclosed in the above-described
Patent Literature 2 in which the guide structure is provided at the
opening of the channel for introducing the sample liquid laminar
flow, the microchip according to the embodiment of the present
invention can be manufactured by the lamination of two substrates
only. The formation of the channel structure onto each substrate
and the lamination of the substrates are thus easy, thereby
suppressing the manufacturing cost of the microchip.
[0118] 9. Particulate Analyzing Device According to Invention
[0119] The above-described microchip can be incorporated into a
particulate analyzing device according to an embodiment of the
present invention. The particulate analyzing device is applicable
as a particulate fractionating device that analyzes the
characteristics of particulates and performs fractionation of
particulates on the basis of the analytical results.
[0120] In the particulate analyzing device, a detector (see the
symbol D in FIG. 15B) for detecting particulates contained in the
sample liquid fed from the sample liquid introduction channel 11 is
placed on the downstream side of the tapered portion 122 or 123 and
the contracted portion 121 in the merge channel 12 of the
microchip.
[0121] The microchip according to the embodiment of the present
invention makes it possible, with the tapered portion 122, 123, to
feed the sample liquid laminar flow S in the state of being
converted to the center of the merge channel 12 and thereby
eliminate the dispersion of the feeding position of the
particulates in the depth direction of the channel and the
difference in the flowing speed of the particulates caused by the
dispersion (see FIG. 2 etc.). Thus, by placing the detecting
portion D on the downstream side of the tapered portion 122, 123
and detecting particulates, it is possible to eliminate the
variation of detection signals caused by the difference in the
flowing speed of the particulates and thereby achieve the detection
of particulates with high accuracy.
[0122] Further, the microchip according to the embodiment of the
present invention makes it possible, with the contracted portion
121, to feed the liquids by narrowing down the laminar flow width
of the sample liquid laminar flow S and the sheath liquid laminar
flow T in the channel width direction and depth direction. By
narrowing down the laminar flow width of the sample liquid laminar
flow S and the sheath liquid laminar flow T, the particulates can
be made to be arranged in a row in the sample liquid laminar flow
S, and the dispersion of the feeding position of the particulates
in the depth direction of the channel and the difference in the
flowing speed of the particulates caused by the dispersion can be
further reduced. Thus, by placing the detecting portion D on the
downstream side of the contracted portion 121 and detecting
particulates, it is possible to detect the particulates one by one
and also make detection by eliminating the variation of detection
signals caused by the difference in the flowing speed of the
particulates as much as possible.
[0123] The detecting portion D may be configured as an optical
detection system, an electrical detection system, or a magnetic
detection system. Those detection systems may be configured in the
same manner as those in particulate analyzing systems using
microchips according to related art. Specifically, the optical
detection system includes a laser beam source, an irradiation
section composed of a condenser lens and the like for condensing
the laser beam and irradiating each of the particulates with the
laser beam, and a detection system for detecting the light
generated from the particulate upon irradiation with the laser beam
by use of a dichroic mirror, a bandpass filter and the like. The
detection of the light generated from particulates may be made by
an area image pick-up element such as a PMT (photo multiplier
tube), a CCD or a CMOS device, for example. Further, the electrical
detection system or the magnetic detection system places
micro-electrodes on the channel of the detecting portion D and
thereby measure, for example, resistance, capacitance, inductance,
impedance, variation in electric field between the electrodes or
the like, or, alternatively, magnetization, variation in magnetic
field or the like.
[0124] The light, resistance, magnetization or the like generated
from the particulates detected in the detecting portion D is
converted into an electrical signal and output to a total control
unit. Note that the light to be detected may be forward scattered
light or side-way scattered light from the particulate, or
scattered light, fluorescent light or the like arising from
Reyleigh scattering, Mie scattering or the like.
[0125] Based on the electrical signal inputted, the total control
unit measures the optical characteristics of the particulates. A
parameter for the measurement of the optical characteristics is
selected according to the particulates under consideration and the
purpose of fractional collection. Specifically, forward scattered
light is adopted in the case of determining the size of the
particulates, side-way scattered light is adopted in the case of
determination of structure, and fluorescent light is adopted in the
case of determining whether a fluorescent material labeling the
particulate is present or absent.
[0126] Further, the particulate analyzing device according to the
embodiment of the present invention may be provided with the
particulate fractionating channel as disclosed in the above Patent
Literature 1 and an electrode for controlling the moving direction
of particulates disposed near a channel port to the particulate
fractionating channel, so as to analyze the characteristics of the
particulates by the total control unit and perform fractionation of
the particulates based on the analytical results.
[0127] The microchip according to the embodiment of the present
invention is easily manufacturable and capable of feeding the
sample liquid laminar flow being converged to the center of the
channel. Therefore, when analyzing the characteristics of
particulates by feeding a solution containing the particulates as a
sample liquid through the channel, high analysis accuracy can be
obtained by eliminating the dispersion of the feeding position of
the particulates in the depth direction of the channel. Therefore,
the microchip according to the embodiment of the present invention
is suitably applicable to the particulate analyzing technology
which analyzes the characteristics of particulates such as cells
and microbeads optically, electrically or magnetically.
[0128] It should be understood that various changes and
modifications to the presently preferred embodiments described
herein will be apparent to those skilled in the art. Such changes
and modifications can be made without departing from the spirit and
scope of the present invention and without diminishing its intended
advantages. It is therefore intended that such changes and
modifications be covered by the appended claims.
* * * * *