U.S. patent application number 13/010142 was filed with the patent office on 2012-07-26 for test device, reaction apparatus and reactive test method.
This patent application is currently assigned to Konica Minolta Holdings, Inc.. Invention is credited to Kusunoki HIGASHINO, Kenichi MIYATA, Yasuhiro SANDO.
Application Number | 20120190129 13/010142 |
Document ID | / |
Family ID | 46544455 |
Filed Date | 2012-07-26 |
United States Patent
Application |
20120190129 |
Kind Code |
A1 |
HIGASHINO; Kusunoki ; et
al. |
July 26, 2012 |
TEST DEVICE, REACTION APPARATUS AND REACTIVE TEST METHOD
Abstract
A test device having a micro flow channel including a reaction
part where a reactant that is reactive to a tested chemical
dispersed in a tested fluid is fixed, and at least one actuator for
actuating the tested fluid to move in at least one of two opposite
sides of the micro flow channel so as to homogenize a density
distribution of the tested chemical in the tested fluid. The tested
fluid is sent in the micro flow channel a plurality of times.
Inventors: |
HIGASHINO; Kusunoki;
(Osaka-shi, JP) ; SANDO; Yasuhiro; (Amagasaki-shi,
JP) ; MIYATA; Kenichi; (Amagasaki-shi, JP) |
Assignee: |
Konica Minolta Holdings,
Inc.
Tokyo
JP
|
Family ID: |
46544455 |
Appl. No.: |
13/010142 |
Filed: |
January 20, 2011 |
Current U.S.
Class: |
436/501 ;
422/81 |
Current CPC
Class: |
B01L 2400/0439 20130101;
B01L 2400/0487 20130101; B01F 11/0266 20130101; B01L 2400/0481
20130101; B01L 2300/088 20130101; B01L 3/50273 20130101; B01L
2400/086 20130101; B01F 15/00876 20130101; B01F 5/0615 20130101;
G01N 33/54366 20130101; B01F 5/102 20130101; G01N 33/54306
20130101; B01F 2005/0633 20130101; B01F 2005/0636 20130101; B01F
11/0071 20130101; B01F 13/0059 20130101 |
Class at
Publication: |
436/501 ;
422/81 |
International
Class: |
G01N 33/53 20060101
G01N033/53; G01N 33/48 20060101 G01N033/48 |
Claims
1. A test device comprising: a micro flow channel including a
reaction part where a reactant that is reactive to a tested
chemical dispersed in a tested fluid is fixed; and at least one
actuator for actuating the tested fluid to move in at least one of
two opposite sides of the micro flow channel so as to homogenize a
density distribution of the tested chemical in the tested fluid;
wherein the tested fluid is sent in the micro flow channel a
plurality of times.
2. A test device according to claim 1, wherein tested fluid
reservoirs that have inner volumes larger than that of the tested
fluid are provided at the two opposite sides of the micro flow
channel.
3. A test device according to claim 2, wherein the at least one
actuator is a stirrer for stirring the tested fluid that is sent to
one of the reservoirs after passing through the reaction part at
least once.
4. A test device according to claim 1, wherein the at least one
actuator is an oscillator.
5. A tested device according to claim 1, wherein the at least one
actuator is a spiral groove.
6. A tested device according to claim 1, wherein the at least one
actuator is steps made spirally.
7. A test device according to claim 1, wherein an immune reaction
between an antigen and an antibody is carried out in the reaction
part.
8. A reaction apparatus comprising: a test device comprising a
reaction part in a micro flow channel, a reactant that is reactive
to a tested chemical dispersed in a tested fluid being fixed in the
reaction part; a fluid sender for sending the tested fluid in the
micro flow channel a plurality of times; and at least one actuator
for actuating the tested fluid to move in at least one of two
opposite sides of the micro flow channel so as to homogenize a
density distribution of the tested chemical in the tested
fluid.
9. A reaction apparatus according to claim 8, wherein the fluid
sender reciprocates the tested fluid in the micro flow channel.
10. A reaction apparatus according to claim 8, wherein the fluid
sender circulates the tested fluid.
11. A reaction apparatus according to claim 8, wherein tested fluid
reservoirs that have inner volumes larger than that of the tested
fluid are provided at the two opposite sides of the micro flow
channel.
12. A reaction apparatus according to claim 11, wherein the at
least one actuator is a stirrer for stirring the tested fluid that
is sent to one of the reservoirs after passing through the reaction
part at least once.
13. A reaction apparatus according to claim 8, wherein the at least
one actuator is an oscillator.
14. A reaction apparatus according to claim 8, wherein the at least
one actuator is a spiral groove.
15. A reaction apparatus according to claim 8, wherein the at least
one actuator is steps made spirally.
16. A reaction apparatus according to claim 8, wherein an immune
reaction between an antigen and an antibody is carried out in the
reaction part.
17. A reactive test method comprising the steps of; sending a
tested fluid in a micro flow channel a plurality of times, the
micro flow channel including a reaction part where a reactant that
is reactive to a tested chemical dispersed in the tested fluid is
fixed; and actuating the tested fluid to move in at least one of
two opposite sides of the micro flow channel so as to homogenize a
density distribution of the tested chemical in the tested
fluid.
18. A reactive test method according to claim 17, wherein the
tested fluid is reciprocated in the micro flow channel.
19. A reactive test method according to claim 17, wherein the
tested fluid is circulated.
20. A reactive test method according to claim 17, wherein the step
of actuating the tested fluid is carried out in a reservoir that is
disposed in at least one of two opposite sides of the micro flow
channel, the reservoir having an inner volume larger than a volume
of the tested fluid.
21. A reactive test method according to claim 17, wherein an immune
reaction between an antigen and an antibody is carried out in the
reaction part.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The .sub.present invention relates to a test device, a
reaction apparatus and a reactive test method, and more
particularly to a test device, a reaction apparatus and a reactive
test method for sending a tested fluid containing a tested
chemical, such as an antigen, in a micro flow channel to cause the
tested chemical to react to a reactant, such as an antibody.
[0003] 2. Description of Prior Art
[0004] FIG. 9 shows a conventional test device comprising a micro
flow channel to subject various kinds of antigens in blood plasma
to reaction to antibodies. In the apparatus shown by FIG. 9, there
is a reaction part 51 wherein a reactant is fixed at the bottom of
a micro flow channel 50, and a tested fluid with a tested chemical
T dispersed therein is sent in the micro flow channel 50 from one
side to the other side (see arrow "A"). In the reaction part 51,
the tested chemical T reacts only around the surface of a
solid-phase layer of the reactant. Therefore, the tested chemical T
flowing in the upper part of the micro flow channel 50 passes
through the micro flow channel 50 without contributing to the
reaction, and the reaction efficiency is bad.
[0005] As a measure to improve the reaction efficiency, it may be
possible to reciprocate the tested fluid in the micro flow channel
so that the part of the tested chemical that did not react first
can be sent back to the reaction part. For example, Japanese Patent
Laid-Open Publication No. 2006-90717 teaches that a tested fluid is
sent back and forth to a reaction part by use of a fluid sending
means such as a pipette. Japanese Patent laid-Open Publication No.
2002-540405 discloses a system and a method for permitting
reversible and controllable flowing of a tested fluid.
[0006] Even in a back-and-forth fluid sending method as described
above, the following problems still remain unsolved. In order to
improve the reaction efficiency by sending a tested chemical closer
to a reaction part, the micro flow channel is preferably as shallow
as possible within a range not to dispute the fluid sending, and
preferably, the depth of the micro flow channel is equal to or less
than 1 mm. Also, in order to prevent the pressure of fluid sending
in the micro flow channel from rising excessively, the flow rate of
the tested fluid is preferably less than several tens of
millimeters per second. In such a fluid sending system, the fluid
moves in laminar flow because Reynolds number is low. Accordingly,
even by reciprocating a tested fluid in the fluid sending system, a
tested chemical does not blend in the tested fluid, and the part of
the tested chemical flowing in the upper part of the micro flow
channel keeps flowing in the upper part. Therefore, even if the
tested fluid is sent back and forth many times, the tested chemical
flowing in the upper part does not contribute to reaction.
[0007] The Reynolds number is an index value that is generally used
in the field of fluid dynamics. The followings are known: if the
Reynolds number is greater than 2000, the flow is turbulent; and if
the Reynolds number is equal to or less than 2000, the flow is
laminar. When the solvent is water based and when the size of the
micro flow channel and the flow rate therein are as above, the
Reynolds number is generally less than 100, and accordingly, the
flow is laminar. Therefore, the reaction efficiency does not
improve unless any special measure is taken.
SUMMARY OF THE INVENTION
[0008] An object of the present invention is to provide a test
device, a reaction apparatus and a reactive test method that permit
improved reaction efficiency in a micro flow channel of a
conventional size.
[0009] In order to attain the object, a test device according to a
first aspect of the present invention comprises: a micro flow
channel including a reaction part where a reactant that is reactive
to a tested chemical dispersed in a tested fluid is fixed; and at
least one actuator for actuating the tested fluid to move in at
least one of two opposite sides of the micro flow channel so as to
homogenize a density distribution of the tested chemical in the
tested fluid; wherein the tested fluid is sent in the micro flow
channel a plurality of times.
[0010] A reaction apparatus according to a second aspect of the
present invention comprises: a test device comprising a reaction
part in a micro flow channel, a reactant that is reactive to a
tested chemical dispersed in a tested fluid being fixed in the
reaction part; a fluid sender for sending the tested fluid in the
micro flow channel a plurality of times; and at least one actuator
for actuating the tested fluid to move in at least one of two
opposite sides of the micro flow channel so as to homogenize a
density distribution of the tested chemical in the tested
fluid.
[0011] A reactive test method according to a third aspect of the
present invention comprises the steps of; sending a tested fluid in
a micro flow channel a plurality of times, the micro flow channel
including a reaction part where a reactant that is reactive to a
tested chemical dispersed in the tested fluid is fixed; and
actuating the tested fluid to move in at least one of two opposite
sides of the micro flow channel so as to homogenize a density
distribution of the tested chemical in the tested fluid.
[0012] In the present invention, "to homogenize a density
distribution of the tested chemical in the tested fluid" does not
necessarily mean to completely homogenize the density distribution
of the tested chemical in the tested fluid, and "actuating the
tested fluid to move so as to homogenize the density distribution
of the tested chemical in the tested fluid" means actuating the
tested fluid to move so that the density distribution of the tested
chemical in the tested fluid will be more even.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] This and other objects and features of the present invention
will be apparent from the following description with reference to
the accompanying drawings, in which:
[0014] FIG. 1 is a sectional view of a test device according to a
first embodiment of the present invention;
[0015] FIG. 2 is a sectional view of a test device according to a
second embodiment of the present invention;
[0016] FIG. 3 is a sectional view of a test device according to a
third embodiment of the present invention;
[0017] FIG. 4 is a front view of a pump used in the third
embodiment;
[0018] FIG. 5 is a sectional view of a test device according to a
fourth embodiment of the present invention;
[0019] FIG. 6 is a sectional view of a spiral groove used in the
fourth embodiment;
[0020] FIG. 7 is a sectional view of a test device according to a
fifth embodiment of the present invention;
[0021] FIG. 8 is a sectional view of a test device according to a
sixth embodiment of the present invention; and
[0022] FIG. 9 is an illustration showing flow of a tested fluid in
a conventional fluid sending system.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0023] Test devices, reaction apparatuses and reactive test methods
according to some embodiments of the present invention are
hereinafter described with reference to the accompanying drawings.
In the drawings, the same parts and the same members are provided
with the same reference numbers, and repetitious descriptions
thereof are omitted.
First Embodiment; See FIG. 1
[0024] A test device 10A according to a first embodiment of the
present invention, as shown in FIGS. 1a and 1b, comprises a micro
flow channel 11, a first reservoir 21 disposed at one end of the
micro flow channel 11, a second reservoir 22 disposed at the other
end of the micro flow channel 11, a waste reservoir 23 connected
directly to the second reservoir 22, and an air inlet/outlet 24. An
air pump 30 is connected to the air inlet/outlet 24. The reservoirs
21 and 22 have inner volumes larger than the volume of a tested
fluid to be sent (shown by cross-hatching in FIG. 1). In the first
embodiment, a combination of the test device 10A and the air pump
30 is referred to as a reaction apparatus.
[0025] In the micro flow channel 11, a reaction part 21 wherein a
reactant that is reactive to a tested chemical dispersed in the
tested fluid is fixed is provided. An oscillator 28 is adhered to a
wall of the first reservoir 21. The oscillator 28 is to stir and
blend the tested fluid in the first reservoir 21 so that the
density of the tested chemical in the tested fluid will be even.
For example, a PZT (a piezoelectric actuator made of lead zirconate
titanate) is suited as the oscillator 28.
[0026] The tested fluid is, for example, blood plasma obtained by
centrifugation of blood collected from a biological object. In this
case, various kinds of antigens in the blood are the tested
chemicals, and antibodies specifically reactive to the antigens are
the reactants fixed in the reaction part 21.
[0027] In the test device 10A according to the first embodiment
10A, the tested fluid is first poured into the reservoir 21. Next,
by operation of the air pump 30, the tested fluid is sent toward
the reservoir 22, that is, sent from the state shown by FIG. 1a to
the state shown by FIG. 1b, and further, the tested fluid is sent
back to the state shown by FIG. 1a. In this way, the tested fluid
is reciprocated in the micro flow channel 11 and passes through the
reaction part 12 a plurality of times, and in the meantime, the
antigens react to the antibodies. While the tested fluid is stored
in the reservoir 21, the oscillator 28 is operated. Thereby, the
tested fluid is stirred so that the antigens can be dispersed in
the tested fluid evenly.
[0028] In the first embodiment, in the reservoir 21 disposed at one
side of the micro flow channel 11, the density distribution of
antigens in the tested fluid is homogenized, and the tested fluid
is sent back and forth in the micro flow channel 11 a plurality of
times. Consequently, the rate of antigens reacting to the
antibodies in the reaction part 21 increases, and the reaction
efficiency is improved.
[0029] Since the inner volumes of the reservoirs 21 and 22 are
larger than the volume of the tested fluid, there is no fear that
the tested fluid may flow out of the reservoirs 21 and 22 even if
the entire tested fluid is sent in the micro flow channel 11
reciprocally. The bottom of the reservoir 21 is bowl shaped, and
the upper portion of the reservoir 21 is wide open. Therefore, when
the tested fluid in the reservoir 21 is vibrated by the oscillator
28, the tested fluid is easy to move, and the stirring efficiency
is good. With respect to the upper opening of the reservoir 21, the
area of the upper opening shall be set as follows so as to obtain a
sufficient effect of a wide opening. Assuming that there is a
sphere having a volume equal to that of the tested fluid, the upper
opening of the reservoir 21 shall be set equal to or greater than
1/10 of the area of the planar projection of the sphere.
[0030] The vibration frequency of the oscillator 28 may be set to
any value. It is, however, preferred for the stirring efficiency
that the vibration frequency of the oscillator 28 is equal to or
nearly equal to the resonance frequency of the tested fluid. The
resonance frequency of the tested fluid may vary depending on the
volume of the tested fluid, and therefore, it is preferred that the
drive frequency of the oscillator 28 is changed in accordance with
changes in the volume of the tested fluid in the reservoir 21 due
to the fluid sending. Alternatively, the drive frequency of the
oscillator 28 may be waved to cause the vibration frequency of the
oscillator 28 to come in resonance with the tested fluid
intermittently. In this case, random motion of the tested fluid is
induced, and mixing of the antigens can be promoted.
[0031] After the tested fluid is reciprocated a predetermined
number of times, the tested fluid is sucked up by the air pump 30
and is thrown away to the reservoir 23. Next, a cleaning solution
is dropped in the reservoir 21 and sent in the micro flow channel
11 by the air pump 30, so that non-reacted antigens remaining in
the reaction part 21 are removed. Thereafter, the surface of the
reaction part 21 is detected optically by a detector (not shown),
and immune reactions between the antigens and the antibodies can be
recognized from changes in the optical characteristics. Such a way
of recognizing an immune reaction is known, and a description
thereof is omitted.
Second Embodiment; See FIG. 2
[0032] A test device 10B according to a second embodiment of the
present invention, as shown in FIG. 2, is basically of the same
structure as the test device 10A according to the first embodiment.
In the test device 10B according to the second embodiment, a cavity
resonator 25 is provided near the reservoir 21. The test device 10B
according to the second embodiment operates in the same way as the
test device 10A according to the first embodiment and has the same
advantages as the test device 10A. In the test device 10B,
especially the cavity resonator 25 amplifies the resonance by the
oscillator 28, thereby resulting in an improvement in the stirring
efficiency of the tested fluid.
Third Embodiment; See FIG. 3
[0033] A test device 10C according to a third embodiment, as shown
in FIG. 3, has a peristaltic tube pump 35 instead of the air pump
30. This tube pump 35 has a tube 38, a center roller 37 and a
plurality of rollers 36 around the center roller 37, and the tube
38 is nipped between a wall 35a and the rollers 36. The rollers 36
are caused to rotate by the center roller 37, and thereby, the
tested fluid in the tube 38 is sent in a direction in accordance
with the rotations of the rollers 36.
[0034] The test device 10C has a reservoir 21 provided with an
oscillator 28 and a micro flow channel 11 including a reaction part
12. One end of the tube 38 is in the reservoir 21, and the other
end of the tube 38 is connected to the opposite end 26 of the micro
flow channel 11 from the reservoir 21. The provision of the tube
pump 35 permits the tested fluid to flow from the reservoir 21 and
to circulate in the micro flow channel 11. Also, the resonance
caused by the oscillator 28 homogenizes the density distribution of
antigens in the tested fluid, and accordingly, the rate of antigens
reacting to the antibodies in the reaction part 12 increases.
Consequently, the reaction efficiency is improved. This fluid
circulating type is especially advantageous when the volume of the
tested fluid is large.
Fourth Embodiment; See FIGS. 5 and 6
[0035] A test device 10D according to a fourth embodiment of the
present invention, as shown in FIG. 5, is basically of the same
structure as the test device 10A according to the first embodiment.
The test device 10D according to the fourth embodiment, however,
has a spiral groove 41 made in an inner wall of the first reservoir
21. As already described in connection with the first embodiment,
the tested fluid is reciprocated between the reservoirs 21 and 22.
According to the fourth embodiment, while the tested fluid flows in
the spiral groove 41 in the first reservoir 21, the tested fluid is
stirred, and the density distribution of the antigens in the tested
fluid is homogenized. It is preferred that the upper opening of the
reservoir 21 is wide so that the stirring of the tested fluid will
be easy. In order to obtain a sufficient effect of a wide opening
of the reservoir 21, the area of the upper opening of the reservoir
21 shall be set equal to or greater than 1/10 of the area of the
planar projection of a sphere having a volume equal to that of the
tested fluid.
[0036] The spiral groove 41 is made by a plate shown by FIG. 6. The
number of turns of the spiral groove 41 may be set arbitrarily. For
efficient stirring of the tested fluid, the width D1 of the groove
41, that is, (the outer diameter D2--the inner diameter D1)/2 is
preferably larger than the pitch H of the spiral groove 41. In the
reservoir 21 of this structure, the flow drag in the spiral groove
41 is smaller than the flow drag in a central hole 42, and
therefore, most part of the tested fluid passes through the groove
41. Accordingly, the stirring efficiency of the tested fluid is
improved.
[0037] As shown in FIG. 6, the cross section of the plate forming
the spiral groove 41 is rectangular. The plate may be disposed to
tilt downward or may have round corners, so that the volume of
residual fluid after a flow-out of the tested fluid can be
reduced.
Fifth Embodiment; See FIG. 7
[0038] A test device 10E according to a fifth embodiment, as shown
in FIG. 7, has a spiral groove 43 made in the inner wall of the
reservoir 21, and a plate forming the spiral groove 43 has a
rectangular cross section with a tapered side near the center of
the reservoir 21. The test device 10E according to the fifth
embodiment operates in the same way as the test device 10A
according to the first embodiment and as the test device 10D
according to the fourth embodiment, and the test device 10E has the
same advantages as the test device 10A and the test device 10D.
Sixth Embodiment; See FIG. 8
[0039] A test device 1OF according to a sixth embodiment, as shown
in FIG. 8, is basically of the same structure as the test device
10A according to the first embodiment. The test device 1OF
according to the sixth embodiment, however, has steps 44 on the
inner wall of the reservoir 21. In the sixth embodiment, the tested
fluid in the reservoir 21 is stirred by the steps 44, and thereby,
the density distribution of the antigens in the tested fluid is
homogenized.
Other Embodiments
[0040] Test devices, reaction apparatuses and reactive test methods
according to the present invention are not limited to the
embodiment above, and various changes and modifications are
possible.
[0041] With respect to reactions at the reaction part, various
kinds of reactions as well as immune reactions between antigens and
antibodies may be carried out. However, in cases of immune
reactions between antigens and antibodies, the molecules of
antigens are of relatively large sizes and are hard to voluntarily
spread, and moving a tested fluid forcibly to homogenize the
density distribution of antigens in the tested fluid as disclosed
by the present invention is very advantageous.
[0042] The oscillator for vibrating the tested fluid is not
necessarily bonded to the test device, and the oscillator may be a
piezoelectric actuator, an electromagnetic actuator or the like
that is laid on the test device from the outside. The oscillator
may be provided for the second reservoir. Alternatively, for both
of the first reservoir and the second reservoir, oscillators may be
provided. Also, the oscillator is not necessarily to vibrate only a
part of the test device but may be to vibrate the test device
entirely.
[0043] With respect to the way of detecting the reaction, as well
as detection by use of optical characteristics, detection by use of
electrical characteristics and visible detection by use of colors
are possible. The detection means may be included in the reaction
apparatus or may be structured separate from the reaction
apparatus. Also, as auxiliary components of an optical detection
system, a lens, a waveguide, a prism, etc. may be incorporated in
the test device.
[0044] Also, in order to improve the detection efficiency, a
fluorescently-labeled substance or the like may be used. More
specifically, in a case of immune reaction between a fixed antibody
(solid-phase antibody) and an antigen, a labeled antibody is
prepared by labeling the antibody that is reactive specifically to
the antigen with a fluorescent substance beforehand.
[0045] Other optional ways are possible. For example, after the
antigen reacts to the solid-phase antibody and is caught in the
reaction part, a solution containing the labeled antibody may be
sent to the reaction part, and thereby, the antigen caught in the
reaction part can be labeled with the fluorescent substance. In
another way, the antigen is caused to react to the
fluorescently-labeled antibody beforehand to generate a
fluorescently-labeled complex, and the complex is sent to the
reaction part so that reaction between the solid-phase antibody and
the antigen can be detected easily. In these cases where a solution
containing the labeled antibody or the labeled complex of the
antigen and the antibody is sent in the micro flow channel, by
homogenizing the density of the labeled antibody or the labeled
complex in the solution during a plurality of reciprocal motions,
the reaction efficiency can be improved.
[0046] There are some optional ways of vibrating the tested fluid
so as to homogenize the density distribution of the tested chemical
in the tested fluid. For example, a stirrer (a magnetic rotator) is
provided in the micro flow channel including the reaction part, in
at least one of the upstream portion or the downstream portion, and
the stirrer is rotated by rotation of a magnet disposed outside of
the test device or by turn on/off of an electric magnet so as to
stir the tested fluid. Magnetic beads may be used instead of the
stirrer.
[0047] In another way, ceramic particles that have a larger
specific gravity than the tested fluid are put in the micro flow
channel including the reaction part, in at least one of the
upstream portion and the downstream portion, and the particles in
the micro flow channel are vibrated by vibrations applied from the
outside of the test device. Further, in another way, an electrode
is disposed in the micro flow channel, in at least one of the
upstream portion and the downstream portion, and an alternating
current is applied to the electrode so as to vibrate ions and other
substances with electric characteristics in the tested fluid. In
this case, when an alternating current is applied to the electrode,
the tested chemical itself, such as an antigen, is moved in the
tested fluid by the electric force.
[0048] Although the present invention has been described in
connection with the preferred embodiments above, it is to be noted
that various changes and modifications are possible to those who
are skilled in the art. Such changes and modifications are to be
understood as being within the scope of the invention.
* * * * *