U.S. patent application number 12/225598 was filed with the patent office on 2009-09-17 for method of reaction in flow channel of microchip and analysis device.
This patent application is currently assigned to KONICA MINOLTA MEDICAL & GRAPHIC, INC.. Invention is credited to Youichi Aoki, Kusunoki Higashino, Akihisa Nakajima, Yasuhiro Sando, Kohsuke Tanimoto.
Application Number | 20090233378 12/225598 |
Document ID | / |
Family ID | 38624767 |
Filed Date | 2009-09-17 |
United States Patent
Application |
20090233378 |
Kind Code |
A1 |
Nakajima; Akihisa ; et
al. |
September 17, 2009 |
Method of Reaction in Flow Channel of Microchip and Analysis
Device
Abstract
In case of performing a reaction between reacting material and
reagent by bringing the reagent in contact with the reacting
material through flowing the reagent into a reaction flow channel
in which the reaction material which reacts with the reagent is
carried on a wall surface of the reaction flow channel of a
microchip, the reaction is expedited efficiently by passing the
reagent to the reacting material. The reagent 30a is flowed such
that a peripheral portion of a gas-liquid interface at a front end
of the reagent moves back and forth on the wall surface of the
reaction flow channel 10 when the reaction is performed.
Inventors: |
Nakajima; Akihisa; (Tokyo,
JP) ; Higashino; Kusunoki; (Osaka, JP) ;
Sando; Yasuhiro; (Hyogo, JP) ; Aoki; Youichi;
(Tokyo, JP) ; Tanimoto; Kohsuke; (Chiba,
JP) |
Correspondence
Address: |
FRISHAUF, HOLTZ, GOODMAN & CHICK, PC
220 Fifth Avenue, 16TH Floor
NEW YORK
NY
10001-7708
US
|
Assignee: |
KONICA MINOLTA MEDICAL &
GRAPHIC, INC.
Tokyo
JP
|
Family ID: |
38624767 |
Appl. No.: |
12/225598 |
Filed: |
February 21, 2007 |
PCT Filed: |
February 21, 2007 |
PCT NO: |
PCT/JP2007/053163 |
371 Date: |
September 25, 2008 |
Current U.S.
Class: |
436/174 ;
422/68.1 |
Current CPC
Class: |
B01L 2200/0673 20130101;
Y10T 436/2575 20150115; Y10T 436/25 20150115; B01L 3/502738
20130101; B01L 2300/0816 20130101; Y10T 436/11 20150115; B01L
3/502784 20130101; B01L 2400/0487 20130101; B01L 3/502723 20130101;
B01L 2400/0688 20130101; G01N 35/1095 20130101; Y10T 436/25375
20150115; B01L 2200/16 20130101; Y10T 436/255 20150115; G01N
2035/00158 20130101; G01N 27/44756 20130101 |
Class at
Publication: |
436/174 ;
422/68.1 |
International
Class: |
G01N 21/00 20060101
G01N021/00; G01N 1/00 20060101 G01N001/00 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 29, 2006 |
JP |
2006-092295 |
Claims
1. A method of reaction in a flow channel of a microchip, which
performs a reaction by bringing reagent in contact with reacting
material by flowing the reagent into a reaction flow channel in
which the reacting material which reacts with the reagent is
carried on a wall surface of the reaction flow channel of the
microchip, wherein the method of reaction comprises flowing the
reagent such that a peripheral portion of a gas-liquid interface at
a front end of the reagent moves back and forth on the wall surface
of the reaction flow channel when the reaction is performed.
2. The method of reaction in the flow channel of the microchip
according to claim 1, wherein, when the reaction is performed,
after the peripheral portion of the gas-liquid interface at the
front end of the reagent passes in a forward direction on the wall
surface of the reaction flow channel and reaches to a flow channel
ahead of the reaction flow channel, an operation is performed at
least once which flows back the reagent such that the peripheral
portion passes in a reverse direction on the wall surface of the
reaction flow channel and then flows the reagent in the forward
direction such that the peripheral portion once again passes in the
forward direction on the wall surface of the reaction flow
channel.
3. The method of reaction in the flow channel of the microchip
according to claim 1, wherein, when a reaction between other
reagent and the reacting material is performed, the method further
comprises: flowing the other reagent which reacts with the reacting
material carried on the wall surface of the reaction flow channel
into the reaction flow channel with intervening gas at a front end
side of the other reagent after the reaction between the reagent
and the reacting material is performed; and flowing other reagent
such that the peripheral portion of the gas-liquid interface at the
front end of the other reagent moves back and forth on the wall
surface of the reaction flow channel.
4. The method of reaction in the flow channel of the microchip
according to claim 3, wherein, when the reaction between the other
reagent and the reacting material is performed, after the
peripheral portion of the gas-liquid interface at the front end of
the other reagent passes in the forward direction on the wall
surface of the reaction flow channel and reaches to a flow channel
ahead of the reaction flow channel, an operation is performed at
least once which flows back the other reagent such that the
peripheral portion passes in the reverse direction on the wall
surface of the reaction flow channel and then flows the other
reagent in the forward direction such that the peripheral portion
once again passes in the forward direction on the wall surface of
the reaction flow channel.
5. The method of reaction in the flow channel of the microchip
according to claim 3, wherein, the microchip comprises, a reagent
holding flow channel which stores the other reagent; a gas storage
flow channel which is disposed at a downstream side of the reagent
holding flow channel, communicates directly or indirectly with the
reaction flow channel at the downstream side thereof, and stores
gas; and a water repellent valve which intervenes between a
downstream end of the reagent holding flow channel and an upstream
end of the gas storage flow channel and includes a flow control
path that has a smaller cross-sectional area than these flow
channels and passes the other reagent forward from the reagent
holding flow channel by applying a flow fluid pressure larger than
a predetermined pressure from an upstream side, wherein, after the
reaction between the reagent and the reacting material is
performed, the reaction between the other reagent and the reacting
material is performed, by pushing the other reagent stored in the
reagent holding flow channel forward from the reagent holding flow
channel through the water repellent valve; flowing the other
reagent into the reaction flow channel with intervening the gas
stored in the gas storage flow channel at the front end of the
other reagent; and, flowing the other reagent such that the
peripheral portion of the gas-liquid interface at the front end of
the other reagent moves back and forth on the wall surface of the
reaction flow channel and the other reagent reacts with the
reacting material.
6. The method of reaction in the flow channel of the microchip
according to claim 1, wherein a flow channel ahead of the reaction
flow channel forms a closed air tight space and the peripheral
portion of the gas-liquid interface at the front end of the reagent
moves back and forth on the wall surface of the reaction flow
channel through reducing a pressure from out side after flowing the
reagent into the reaction flow channel by the pressure.
7. The method of reaction in the flow channel of the microchip
according to claim 6, wherein a volume of the closed flow channel
ahead of the reaction flow channel is larger than a volume of the
reaction flow channel.
8. The method of reaction in the flow channel of the microchip
according to claim 6, wherein a gas vent channel which has an end
opened to an outer atmosphere is provided at a position before the
reaction flow channel.
9. An analysis device to which is loaded a microchip which includes
a reaction flow channel in which a reacting material which reacts
with a reagent is carried on a wall surface of the flow channels,
and in which a reaction is performed by flowing the reagent into
the reaction flow channel so that the reagent contacts and reacts
with the reacting material, wherein the analysis device comprises a
liquid flowing unit which flows the reagent such that a peripheral
portion of the gas-liquid interface at a front end of the reagent
moves back and forth on the wall surface of the reaction flow
channel when the reaction is performed.
Description
TECHNICAL FIELD
[0001] The present invention relates to a method of reaction in a
flow channel of microchip and an analysis device. More specifically
the present invention relates to a method of reaction between a
reacting material carried on an inner surface of the wall of the
flow channel (simply called reacting material hereinafter) and the
reagent in the flow channel by flowing the reagent into the flow
channel and contacting the reagent with the reacting material and
related to an analysis device.
BACKGROUND ART
[0002] In recent years, due to the use of micro-machine technology
and microscopic processing technology, systems are being developed
in which devices and means (for example pumps, valves, flow
channels, sensors and the like) for performing conventional sample
preparation, chemical analysis, chemical synthesis and the like are
miniaturized and integrated on a single chip (Patent Document 1).
These systems are called .mu.-TAS (Micro Total Analysis System),
bioreactor, lab-on-chips, and biochips, and are much expected to be
applied in the fields of medical testing and diagnosis,
environmental measurement and agricultural manufacturing.
[0003] The quantitative performance of analysis, accuracy of
analysis and economic efficiency in these types of analysis and
testing are considered important when using these types of chips
for analysis. (These types of chips which have micro flow channels
and in which various reactions are performed in the micro flow
channels are called microchips.) As a result, it is an issue to
provide a feeding system which has a simple structure and is highly
reliable. A micro fluid control device which has high accuracy and
excellent reliability is required. Micro-pump systems and control
methods which meet this need have already been proposed. (Patent
Documents 2-4)
[0004] Patent Document 1: Unexamined Japanese Patent Application
No. 2005-323519
[0005] Patent Document 2: Unexamined Japanese Patent Application
No. 2001-322099
[0006] Patent Document 3: Unexamined Japanese Patent Application
No. 2004-108285
[0007] Patent Document 4: Unexamined Japanese Patent Application
No. 2004-270537
DISCLOSURES OF THE INVENTION
Problems to be Solved by the Invention
[0008] The inventors of the present invention have been studying on
microchips for performing amplification and detection of specific
genes in a specimen with high sensitivity. In this type of
microchip, in some cases the reacting material is carried on the
wall surface of the flow channel inside the chip and a reaction is
performed when a plurality of reagents are flowed in sequence into
the flow channel, thereby bringing sequentially the reagents in
contact with the reacting material carried.
[0009] More specifically, for example, gene amplification is
performed in the flow channel of the microchip using biotinylated
primer; then the amplified gene is denatured to form a single
strand and is fed into a flow channel for detection in which a
biotin affinity protein such as streptavidin is absorbed and fixed
onto the wall formed of polystyrene and the like; then the gene is
fixed on the wall of the flow channel by the bonding reaction of
biotin affinity protein and the biotin; then a probe DNA whose end
has been fluorescently labelled with FITC (fluorescein
isothiocyanate) is flowed into the flow channel and hybridized with
the fixed gene; then the gold colloid whose surface has been
modified with an FITC antibody which bonds specifically with FITC
is flowed into the flow channels; and then the gold colloid is
adsorbed by the FITC modified probe that has been hybridized with
the gene. The amplified gene is detected high-sensitively by
optically measuring the concentration of the adsorbed gold
colloid.
[0010] In the micro flow channel formed in a substrate of the
microchip, a flow velocity in fluid flow forms a gradient in the
direction perpendicular to the flow channel and the flow velocity
decreases as approaching to the wall surface of the flow channel.
In the vicinity of the wall surface of the flow channel, the fluid
flow velocity is substantially 0. As a result, when the reaction is
to be performed by flowing a reagent into the flow channel in which
the reacting material is carried on the wall surface of the flow
channel as in the case above, even when the reagent is flowed into
the flow channel, the reagent stays at the wall surface vicinity
and does not flow and thus it is difficult to continue supplying
reagent to reacting material such as the amplified gene carried on
the wall surface of the flow channel and the reaction does not
progress. Even in the case where other reagents are successively
forced into the flow channel to carry out the reaction, when the
different fluids including the various reagents are flowed
continuously, a portion of the previous fluid remains on the wall
surface and because the previous fluid is not replaced with the
next fluid, the reaction does not progress.
[0011] It is to be noted that Patent Document 1 discloses
technology in which in a micro fluid device for testing a reagent
by flowing the reagent into the flow channel formed in a chip and
gas in injected between the reagent and the drive fluid for pushing
and sending the reagent driven by the micropump from the upstream
side such that the reagent and the drive fluid do not come in
direct contact with each other. However, the technology disclosed
in this document causes reduction in the amount of reagent due to
the placement of gas between the reagent and the driving fluid, but
there is no mention about the present invention.
[0012] The object of the present invention is to speed up the
progress of the reaction by allowing efficient flow of the reagent
into the reacting material when the reacting material and the
reagent are brought in contact with each other and react by flowing
the reagent into the reaction flow channel in which the reacting
material is carried on the wall surface of the flow channel formed
in a substrate of the microchip.
Means for Solving the Problem
[0013] The method of reaction of microchip in a flow channel
disclosed in the present invention is a reaction method in which a
reaction is performed by bringing the reagent in contact with the
reaction by flowing the reagent into the reaction flow channel in
which the reacting material which reacts with the reagent is
carried on the wall surface of the flow channel of the microchip,
wherein the reagent is fed such that at the time when the reaction
is performed, the peripheral portion of the gas-liquid interface in
the front end of the reagent moves back and forth on the wall
surface of the reaction flow channel.
[0014] In a preferable aspect of the invention above, when the
reaction is performed, an operation of flowing the reagent is
performed at least once such that the peripheral portion of the
gas-liquid interface in the front end of the reagent passes in the
forward direction on the wall surface of the reaction flow channel,
then the peripheral portion passes in the reverse direction on the
wall surface of the reaction flow channel after reaching to a flow
channel ahead of the reaction flow channel, and then the peripheral
portion once again passes in the forward direction on the wall
surface of the reaction flow channel.
[0015] Furthermore, in the method of reaction of microchip in a
flow channel disclosed in the present invention, after the reaction
between the reagent and the reacting material is performed, the
other reagent that reacts with the reacting material carried in the
reaction flow channel is flowed into the reaction flow channel
through the intervening gas space at the front end side of the
reacting material, such that, when the reaction of other reagent is
performed, the peripheral portion of the gas-liquid interface at
the front end of the other reagent moves back and forth on the wall
surface of the reaction flow channel.
[0016] In a preferable aspect of the above invention, when the
reaction between the other reagent and the reacting material is
performed, an operation is performed at least once, such that the
peripheral portion of the gas-liquid interface at the front end of
the other reagent passes on the wall surface of the reaction flow
channel in the forward direction, then the peripheral portion
passes in the reverse direction on the wall surface of the reaction
flow channel after reaching to a flow channel ahead of the reaction
flow channel, and then the peripheral portion once again passes in
the forward direction on the wall surface of the reaction flow
channel.
[0017] In another preferable aspect of this invention, the
microchip comprises:
[0018] a reagent holding flow channel in which the other reagent is
stored;
[0019] a gas storage flow-channel which is disposed at the
downstream side of the reagent holding flow channel and
communicates directly or indirectly with the reaction flow channel
at the downstream side;
[0020] a water repellent valve which is arranged between the
downstream end of the reagent holding flow channel and the upstream
end of the gas storage flow channel and includes a feed control
flow channel that has a smaller cross-sectional area than these
flow channels and which passes the other reagent forward from the
reagent holding flow channel by applying fluid flow pressures
larger than a predetermined pressure from the upstream side;
wherein
[0021] after the reaction between the reagent and the reacting
material is performed, the other reagent stored in the reagent
holding flow channel is pushed to the front from the reagent
holding flow channel through the water repellent valve and the
other reagent is fed into the reaction flow channel through the
intervening gas space at the front end of the other reagent, and is
flowed such that the peripheral portion of the gas-liquid interface
at the front side of the other reagent moves back and forth on the
wall surface of the reaction flow channel to react the other
reagent with the reacting material.
[0022] In the invention above, the flow channel ahead of the
reaction flow channel forms a closed air tight space. It is
preferred that the peripheral portion of the gas-liquid interface
at the front end of the reagent moves back and forth on the wall
surface of the reaction flow channel by reducing the pressure after
the reagent is flowed into reaction flow channel by pressure from
the outside.
[0023] In this case, the volume of the closed flow channel ahead of
the reaction flow channel is preferably larger than the volume of
the reaction flow channel.
[0024] Furthermore, it is preferable to provide a gas vent channel
which has an end which is opened to an outer atmosphere is provided
at a position before the reaction flow channel.
[0025] The analysis device of the present invention to which is
loaded a microchip which includes a reaction flow channel in which
a reacting material which reacts with a reagent is carried on the
wall surface of the flow channels, and in which a reaction is
performed by feeding the reagent into reaction flow channel and
bring the reagent in contact with the reacting material;
[0026] and the analysis device comprises a feeding means which
flows the reagent such that, when the reaction is performed, the
peripheral portion of the gas-liquid interface at the front end of
the other reagent moves back and forth on the wall surface of the
reaction flow channel.
[0027] According to the present invention, the meniscus is moved
back and forth on the wall surface of the reaction flow channel in
which the reacting material that reacts with the reagent is
carried, and thus separation of the reagent from the wall surface
as well as new contact of the reagent with the wall surface
progresses due to multiple passages of the gas-liquid interface,
and substitution of the reagent on the wall surface of the flow
channel is effectively performed and thus reaction progress is sped
up.
[0028] By configuring the flow channel ahead of the reaction flow
channel as a closed air tight flow channel, the reagent is flowed
by pressure into the reaction flow channel, then the reagent is
pushed back to the reaction flow channel as the gas space in the
closed flow channel has been compressed by the reagent when the
liquid feed pressure is released, and in this manner, the reagent
is caused to move back and forth.
EFFECTS OF THE INVENTION
[0029] According to the present invention, the reagent effectively
circulates to the reacting material which reacts with the reagent
and is carried on the wall surface of the flow channel of the
microchip, and the progress of the reaction can be sped up.
BRIEF SUMMARY OF THE DRAWINGS
[0030] FIG. 1 shows an example of the overall structure of
microchip used in the present invention and the control device
thereof.
[0031] FIG. 2 is an explanatory drawing for the flowing of the
first reagent into the reaction flow channel in which the reacting
material is carried in the first embodiment of this invention
[0032] FIG. 3 is an explanatory drawing for the flowing of the
first reagent into the reaction flow channel in which the reacting
material is carried in the first embodiment of this invention.
[0033] FIG. 4 is an explanatory drawing for the flowing of the
first reagent into the reaction flow channel in which the reacting
material is carried in the first embodiment of this invention.
[0034] FIG. 5 is an explanatory drawing for the flowing of the
first reagent into the reaction flow channel in which the reacting
material is carried in the first embodiment of this invention.
[0035] FIG. 6 is an explanatory drawing for the flowing of the
first and second reagents into the reaction flow channel in which
the reacting material is carried in the second embodiment of this
invention.
[0036] FIG. 7 is an explanatory drawing for the feeding of the
first and second reagent into the reaction flow channel in which
the reacting material is carried in the second embodiment of this
invention.
[0037] FIG. 8 is an explanatory drawing for the flowing of the
first and second reagents into the reaction flow channel in which
the reacting material is carried in the second embodiment of this
invention.
[0038] FIG. 9 is an explanatory drawing for the flowing of the
first and second reagents into the reaction flow channel in which
the reacting material is carried in the second embodiment of this
invention.
[0039] FIG. 10 is an exploded view of the water repellent
valve.
[0040] FIG. 11 is an explanatory drawing for the flowing of the
first to third reagents into the reaction flow channel in which the
reacting material is carried in the third embodiment of this
invention.
[0041] FIG. 12 shows the flow channel for describing the modified
example of the third embodiment.
DESCRIPTION OF REFERENCE NUMERALS
[0042] 1 Microchip [0043] 2 Analysis device [0044] 10 Reaction flow
channel [0045] 10a Wall surface [0046] 21 Flow channel [0047] 22
Flow channel [0048] 30a First reagent [0049] 30b Second reagent
[0050] 30c Third reagent [0051] 31 Front end of reagent (Gas-liquid
interface) [0052] 35 Drive fluid [0053] 40a, 40b Reagent holding
flow channel [0054] 50a, 50b Gas storage flow channel [0055] 60
Water repellent valve [0056] 61 Feed control channel [0057] 62a,
62b Flow channel [0058] 63 Fluid [0059] 71 First reagent flow
channel [0060] 72 Common flow channel [0061] 81a, 81b Drive fluid
injection port [0062] 82a, 82b Drive fluid flow channel [0063] 83a,
83b Gas vent channel
PREFERABLE EMBODIMENTS OF THE INVENTION
[0064] Embodiments of the present invention will be described in
the following with reference to the drawings. In the microchip used
in the present invention, with the aims of various tests, chemical
analysis, chemical synthesis, sample processing and separation,
reactions using reagents are performed on the micro flow channels
provided inside the plate-like chip.
[0065] In the present invention, the application of the microchip
includes biological testing and analysis by gene amplification
reaction and antigen-antibody reaction. The invention is also used
for chemical testing and analysis, chemical synthesis of target
compound by organic synthesis, drug screening, drug effect
screening, drug extraction and formation and separation of metal
complexes.
[0066] In the following embodiment, the example is given in which a
specimen is injected into the flow channel formed in the microchip
and mixed with the amplification reagent in the flow channel to
perform gene amplification, then the amplified gene is fixed and
detected in the downstream flow channel. As shown in FIG. 1, the
microchip is a plate shaped chip that is made of a material such as
resin and micro flow channels are provided inside the chip. Various
fluids such as reagents are flowed into the injection port provided
at the upstream side of the microchip 1 by injecting drive fluid
that is driven by liquid flowing means such as an independent drive
pump, and by moving the drive fluid in the forward and reverse
direction by a micropump. The microchip 1, the temperature control
device, the optical detection device and the like are incorporated
into the analysis device 2, and by loading the microchip 1 into the
analysis device 2, the series of analysis operation can be
performed automatically.
[0067] After the microchip 1 is loaded into the analysis device 2,
the biotin modified primer is used to amplify the gene in the flow
channel of the microchip 1 and the amplified gene is denatured to
form a single strand. The resultant solution (called first reagent
hereinafter) is flowed into the flow channel on the wall of which a
biotinophilic protein such as streptavidin is carried and fixed.
The gene is fixed in the wall of the flow channel due to the
bonding reaction between the biotinophilic protein and the
biotin.
[0068] Next, a probe DNA (called second reagent hereinafter) whose
end has been fluorescently labelled with FITC is flowed into the
flow channel and hybridized with the fixed gene.
[0069] The solution of the gold colloid (called third reagent
hereinafter) whose surface has been modified with an anti-FITC
antibody which bonds specifically with FITC flowed into the flow
channels and the gold colloid is adsorbed to the FITC modified
probe that has been hybridized with the gene. The amplified gene is
detected by optically measuring the concentration of the adsorbed
gold colloid.
[0070] It is to be noted that the reacting material in the
description below that is carried in the flow channel wall refers
to the biotinophilic protein, the gene that has bonded with the
biotinophilic protein, or the DNA probe that has been hybridized
with the gene.
First Embodiment
[0071] FIG. 2-FIG. 5 are explanatory drawings for the flowing of
the first reagent into the reaction flow channel in which the
reacting material is carried in the first embodiment of this
invention. In these drawings, 10 denotes the reaction flow channel
that has the reacting material carried on its wall surface. By
flowing the first reagent 30a into the reaction flow channel 10,
the first reagent 30a is brought in contact with the reacting
material and the reaction is performed.
[0072] The operation of feeding the first reagent 30a at the time
of reaction will be described sequentially in the following. First
as shown in FIG. 2, the first reagent 30a is supplied to the
reaction flow channel 10 through the upstream flow channel 21 of
the reaction flow channel 10.
[0073] When the front end 31 of the first reagent 30a is put into
the reaction flow channel 10, as shown in FIG. 3, the peripheral
portion of the gas-liquid interface in the front end 31 of the
first reagent 30a passes in the forward direction on the wall
surface of the reaction flow channel.
[0074] When feeding of the first reagent 30a continues, as shown in
FIG. 4, the front end 31 of the first reagent 30a passes through
the reaction flow channel 10 and reaches to the flow channel 22
ahead of the flow channel 10.
[0075] In this manner, the reaction flow channel 10 is filled with
first reagent 30a and then the first reagent 30a is flowed back in
the reverse direction such that the front end 31 of the first
reagent 30a is put into the reaction flow channel 10 again as shown
in FIG. 5 and the peripheral portion of the gas-liquid interface at
the front end 31 of the first reagent 30a passes in the reverse
direction on the wall surface 10a of the reaction flow channel
10.
[0076] Subsequently, as same as shown in FIG. 3, the reagent is
flowed once again from the state where the front end 31 of the
first reagent 30a is positioned in the reaction flow channel 10 or
in the upstream flow channel 21 of the reaction flow channel 10 so
that the peripheral portion of the gas-liquid interface at the
front end 31 passes through in the forward direction on the wall
surface 10a of the reaction flow channel 10.
[0077] In this embodiment, the feeding operation is performed at
least once, or preferably performed multiple times. Because the
peripheral portion of the gas-liquid interface at the front end 31
of the first reagent 30a is moved back and forth and passes a
plurality of times on the wall surface 10a of the reaction flow
channel 10, movement of the fluid occurs on the wall surface 10a
each time the first reagent 30a passes through and thus the
situation where the first reagent 30a does not flow and constantly
accumulates is prevented. As a result, new contact of the first
reagent 30a with the reacting material that is carried on the wall
surface 10a progresses and substitution of the reagent with the
reacting material on the wall surface 10a is effectively performed.
Thus the progress of the reaction is sped up.
Embodiment 2
[0078] FIG. 6-FIG. 9 are explanatory drawings for the flowing of
the first and second reagent into the reaction flow channel on
which the reacting material is carried in the second embodiment of
this invention. It is to be noted that in these drawings, the
structural elements which are the same as those in the first
embodiment have been assigned the same numbers and descriptions
thereof have been omitted.
[0079] In this embodiment, the operation is repeated in which the
first reagent 30a is flowed into the reaction flow channel 10 and
caused to react with the reacting material that is fixed on the
flow channel wall and then the second reagent 30b is flowed into
the reaction flow channel 10 and caused to react with the reacting
material that is fixed on the flow channel wall.
[0080] As shown in FIG. 6, the second reagent 30b is stored in the
reagent holding flow channel 40a. A water repellent valve 60 is
provided respectively on the upstream end and the downstream end of
the reagent holding flow channel 40a, and the second reagent 30b is
held in the reagent holding flow channel 40a by these water
repellent valves 60.
[0081] FIG. 10 is an exploded view of the water repellent valve.
The water repellent valve 60 in FIG. 10 comprises a flow control
channel 61 which has a narrow flow channel width. The
cross-sectional area (the cross-sectional area of a vertical
cross-section of the flow channel) is smaller than that of the
upstream flow channel 62a and the downstream flow channel 62b.
[0082] In the case where the flow channel wall is formed of a
hydrophobic material such as resin and the like, passage into the
downstream flow channel 62b of the fluid 63 that is in contact with
the feed control channel 61 is controlled by the difference in
surface tension with respect to the flow channel wall.
[0083] A flow fluid pressure exceeding a predetermined pressure is
applied by the micropump in order to cause the fluid 63 to flow out
to the downstream flow channel 62b, and as a result, the fluid 63
resists the surface tension and is expelled from the feed control
flow channel 61 to the downstream flow channel 62. After the fluid
63 flows out to the flow channel 62b, even if the feed pressure
required to expel the front end of the fluid 63 to the downstream
flow channel 62b is not maintained, fluid flows to the downstream
flow channel 62b.
[0084] That is to say, passage of the fluid forward from the feed
control flow channel 61 is blocked until the feed pressure in the
forward direction from the upstream side to the downstream side
reaches a predetermined pressure, and by applying fluid feed
pressure exceeding the predetermined pressure, fluid 63 passes
through the feed control flow channel 61. One example is the case
where feed control flow channel 61 is formed so the width by depth
is 25 .mu.m.times.25 .mu.m for the flow channels 62a and 62b with
width by depth of 150 .mu.m.times.300 .mu.m
[0085] As shown in FIG. 6, a gas storage flow channel 50a is
provided by intervening the water repellent valve 60 at the
downstream side of the reagent holding flow channel 40a. The first
reagent flow channel 71 merges with the gas storage flow channel
50a at the downstream end of the gas storage flow channel 50a, and
the gas storage flow channel 50a, communicates with the common flow
channel 72.
[0086] The following is a sequential description of the flowing
operations when the first and the second reagents are caused to
react with the reacting material. First, from the state shown in
FIG. 6, the first reagent 30a is supplied from the reagent flow
channel 71 to the reaction flow channel 10 through the common flow
channel 72.
[0087] Then, as shown in FIG. 7, after the front end of the first
reagent 30a is moved into the reaction flow channel 10, in the same
sequence as that of the first embodiment, the front end moves in
the forward and reverse directions between the reaction flow
channel 10 and the flow channel 22 ahead thereof. As a result, the
peripheral portion of the gas-liquid interface in the front end of
the first reagent 30a passes multiple times on the wall surface of
the reaction flow channel 10 on which the reacting material is
carried, and thus, new supply and contact of the first reagent 30a
with the reacting material that is carried on the wall surface 10a
progresses and the reaction is performed.
[0088] Next as shown in FIG. 8, the second reagent 30b that is
stored in the reagent holding flow channel 40a is expelled from the
upstream side by the drive fluid 35 that is driven by the micropump
(not shown) and pressure exceeding the fluid holding pressure of
the water repellent valve 60 is applied and the second reagent 30b
is expelled to the gas storage flow channel 50a. As a result, the
gas that is stored in the gas storage flow channel 50a is pushed
out to the common flow channel 72 side and the second reagent 30b
is flowed to the reaction flow channel 10 in a state where the gas
intervenes at the front end of the second reagent 3b.
[0089] As shown in FIG. 9, after the front end of the second
reagent 30b is put into the reaction flow channel 10, in the same
sequence as above, the front end moves in the forward and reverse
direction between the reaction flow channel 10 and the flow channel
22 ahead thereof. This causes the peripheral portion of the
gas-liquid interface at the front end of the second reagent 30b to
pass multiple times on the wall surface of the reaction flow
channel 10 which carries the reacting material. Thus, the reacting
material carried on the wall surface reacts with the second reagent
30b while accelerating new supply and contact of the second reagent
30b with the reacting material.
[0090] As described above, this embodiment allows gas to intervene
at the front end of the second reagent 30b, which can accelerate
the reaction while moving back and forth the gas-liquid interface
at the front end on the wall surface of the reaction flow channel
10, as the case with the first reagent 30a and the second reagent
30b.
Third Embodiment
[0091] FIG. 11 is an explanatory drawing for the flowing of the
first to third reagents into the reaction flow channel on which the
reacting material is carried in the third embodiment of this
invention.
[0092] In FIG. 11, the structural elements which are the same as
those in the above embodiments have been assigned the same numbers
and descriptions thereof have been omitted.
[0093] In this embodiment, the first reagent 30a is flowed into the
reaction flow channel 10 and caused to react with the reacting
material that is fixed in the flow channel wall and then the second
reagent 30b is flowed into the reaction flow channel 10 and caused
to react with the reacting material that is fixed in the flow
channel wall. After this the third reagent 30c is flowed into the
reaction flow channel 10 and caused to react with the reacting
material that is fixed in the flow channel wall.
[0094] As shown in FIG. 11, the second reagent 30b is stored in the
reagent holding flow channel 40a and the third reagent 30c is
stored in the reagent holding flow channel 40a. A water repellent
valve 60 is provided on the upstream end and the downstream end
respectively of the reagent holding flow channel 40a, and the
second reagent 30b is held in the reagent holding flow channel 40a
by these water repellent valves 60. Similarly, the third reagent
30c is held in the reagent holding flow channel 40b by two water
repellent valves 60
[0095] A gas storage flow channel 50a is provided at the downstream
side of the reagent holding flow channel 40a through the water
repellent valve 60. The gas storage flow channel 50a merges with
the first reagent flow channel 71 at the downstream end of the gas
storage flow channel 50a and communicates with the common flow
channel 72. Similarly, the gas storage flow channel 50b is provided
at the downstream side of the reagent holding flow channel 40b
through the water repellent valve 60. The gas storage flow channel
50b merges with the first reagent flow channel 71 at the downstream
end of the gas storage flow channel 50b and communicates with the
common flow channel 72.
[0096] The following is a description in sequence of the feeding
operation when the first to third reagents are reacted with the
reacting material. First, the first reagent 30a is supplied from
the first reagent flow channel 71 to the reaction flow channel 10
through the common flow channel 72 and after the front end of the
first reagent 30a is moved into the reaction flow channel 10, in
the same sequence as that of the first embodiment, the front end
moves in the forward and reverse directions between the reaction
flow channel 10 and the flow channel 22 in the front thereof. This
causes the peripheral portion of the gas-liquid interface at the
front end of the first reagent 30a to pass multiple times on the
wall surface of the reaction flow channel 10 which carries the
reacting material. Thus, the reacting material carried on the wall
surface reacts with the second reagent 30b while accelerating new
supply and contact of the first reagent 30a with the reacting
material.
[0097] Next, drive fluid is injected from the drive fluid injection
port 81a in the chip that communicates with the micropump (not
shown), the injection port being the opening provided upstream of
the drive fluid flow channel 82a. The second reagent 30b that is
stored in the reagent holding flow channel 40a is pushed from the
upstream side and pressure exceeding the fluid holding pressure of
the water repellent valve 60 is applied and the second reagent 30b
is expelled to the downstream side. It is to be noted that 83a is a
gas vent channel for removing gas bubbles between the drive fluid
injected from the drive fluid injection port 81a and the second
reagent 30b to the outside. More specifically, 83a is a narrow flow
channel that controls the passage of fluid inside the flow channel
due to water repellent property or high flow channel resistance and
which has an end for removing gas bubbles from the inside of the
flow channel to the outside.
[0098] As a result, the gas that is stored in the gas storage flow
channel 50a is pushed out to the common flow channel 72 side and
the second reagent 30b is fed to the reaction flow channel 10 in a
state where the gas intervenes, at the second reagent 30b front end
side. After the front end of the second reagent 30b is moved into
the reaction flow channel 10, in the same sequence as above, the
front end moves in the forward and reverse directions between the
reaction flow channel 10 and the flow channel 22 ahead thereof.
This causes the peripheral portion of the gas-liquid interface at
the front end of the second reagent 30b to pass multiple times on
the wall surface of the reaction flow channel 10 which carries the
reacting material. Thus, the reacting material carried on the wall
surface reacts with the second reagent 30b while accelerating new
supply and contact of the second reagent 30b with the reacting
material.
[0099] Next, drive fluid is injected from the drive fluid injection
port 81b and the third reagent 30c that is stored in the reagent
holding flow channel 40b is pushed from the upstream side and
pressure exceeding the fluid holding pressure of the water
repellent valve 60 is applied and the third reagent 30c is pushed
out to the downstream side.
[0100] As a result, the gas that is stored in the gas storage flow
channel 50a is expelled to the common flow channel 72 side and the
third reagent 30c is flowed to the reaction flow channel 10 in a
state where the gas intervenes at the third reagent 30c front end
side. After the front end of the third reagent 30c is moved into
the reaction flow channel 10, in the same sequence as above, the
front end moves in the forward and reverse directions between the
reaction flow channel 10 and the flow channel 22 ahead thereof.
This causes the peripheral portion of the gas-liquid interface at
the front end of the second reagent 30b to pass multiple times on
the wall surface of the reaction flow channel 10 which carries the
reacting material. Thus, the reacting material carried on the wall
surface reacts with the third reagent 30c while accelerating new
supply and contact of the third reagent 30c with the reacting
material.
[0101] As described above, when the first to third reagents are
flowed to the reaction flow channels, gas is allowed to intervene,
thus making it possible to accelerate the reaction of these regents
with the reacting material while moving back and forth the
gas-liquid interface at the front end of the reaction flow channel
10 on the wall surface of the reaction flow channel 10.
[0102] FIG. 12 shows the flow channel for describing the modified
example of the third embodiment. In this modified example, the
common flow channel 72 is not provided as in FIG. 11 and the gas
storage flow channels 50a and 50b are directly connected to the
reaction flow channels respectively. Even when the flow channel is
structured in this manner, the feeding operation is performed in
the same manner as described in the third embodiment, and the first
to third reagents are flowed to the reaction flow channel 10 in a
state where the gas intervenes at each front end of the first to
third reagents. This can accelerate the reaction by passing multi
times the peripheral portion of the gas-liquid interface on the
wall surface of the reaction flow channel 10 in which the reacting
material is fixed.
[0103] The invention has been described based on these embodiments,
but the invention is not to be limited by these embodiments, and
various changes and modifications are possible provided that they
do not depart from the scope of the invention.
[0104] For example, by configuring the flow channel 22 as a closed
airtight space from the point of the reaction flow channel 10
forward, reagent is flowed to the reaction flow channel 10 by the
fluid feeding micropump and then the reagent returns to the
reaction flow channel 10 side when pressure falls due to the
driving of the micropump being stopped, because the gas space
inside the flow channel 22 is compressed by the reagent. As a
result, the flow channel 22 with the closed end acts as a damper
and the reagent is able to move back and forth inside the reaction
flow channel 10.
[0105] In this case, the gas vent channel 83a (83b) is preferably
provided at a position before of the reaction flow channel 10 as
shown in FIG. 11. By providing this gas vent channel, after the
reagent is pressure-flowed to the reaction flow channel 10 using
the micropump for flowing fluid, by stopping the micropump, the
reagent returns to the reaction flow channel 10 side and the front
end of the reagent returns to the position of the gas vent channel
where the gas is vented to the atmosphere because the gas space in
the flow channel 22 described above is compressed by the reagent.
As a result, the complex control of the micropump is not necessary
and the reagent can easily move back and forth inside the reaction
flow channel 10.
* * * * *