U.S. patent application number 12/304077 was filed with the patent office on 2010-09-16 for micro total analysis system equipped with leakage prevention mechanism.
This patent application is currently assigned to KONICA MINOLTA MEDICAL & GRAPHIC, INC.. Invention is credited to Youichi Aoki, Kusunoki Higashino, Akihisa Nakajima, Yasuhiro Sando.
Application Number | 20100232986 12/304077 |
Document ID | / |
Family ID | 38831560 |
Filed Date | 2010-09-16 |
United States Patent
Application |
20100232986 |
Kind Code |
A1 |
Sando; Yasuhiro ; et
al. |
September 16, 2010 |
MICRO TOTAL ANALYSIS SYSTEM EQUIPPED WITH LEAKAGE PREVENTION
MECHANISM
Abstract
A micro total analysis system, comprising: an examination chip
provided with a micro flow path and a flow path opening section
communicating with a micropump on the upstream side of a reagent
containing section, a drive fluid tank containing drive fluid, a
micropump unit provided with a plurality of the micropumps such
that the upstream side of each micropump communicates with the
drive fluid tank and a flow path opening communicating with the
micro flow path of the examination chip is provided on the
downstream side, and a system body including the micropump unit and
the drive fluid tank in one storing body, wherein analysis is
performed while the examination chip is attached to the system
body, and a mechanism for altering the direction of pressure at the
flow path opening of the micropump unit depending on
attaching/detaching of the examination chip to/from the system main
body is provided.
Inventors: |
Sando; Yasuhiro; (Hyogo,
JP) ; Nakajima; Akihisa; (Tokyo, JP) ;
Higashino; Kusunoki; (Osaka, JP) ; Aoki; Youichi;
(Tokyo, JP) |
Correspondence
Address: |
CANTOR COLBURN, LLP
20 Church Street, 22nd Floor
Hartford
CT
06103
US
|
Assignee: |
KONICA MINOLTA MEDICAL &
GRAPHIC, INC.
Tokyo
JP
|
Family ID: |
38831560 |
Appl. No.: |
12/304077 |
Filed: |
May 8, 2007 |
PCT Filed: |
May 8, 2007 |
PCT NO: |
PCT/JP2007/059496 |
371 Date: |
December 9, 2008 |
Current U.S.
Class: |
417/63 |
Current CPC
Class: |
G01N 35/08 20130101 |
Class at
Publication: |
417/63 |
International
Class: |
F04B 49/00 20060101
F04B049/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 12, 2006 |
JP |
2006-162778 |
Claims
1. A micro total analysis system, comprising: an examination chip
provided with a succession of a micro flow path and a flow path
opening section at an upstream side of a containing position of a
reagent in the micro flow path, wherein the flow path opening
section is communicated with a micropump; a drive fluid tank to
contain a drive fluid which pushes the reagent the upstream side to
a downstream side of the micro flow path of the examination chip; a
micropump unit provided with a plurality of the micropumps on a
surface of a chip, wherein an upstream side of each micropump is
communicated with the drive fluid tank and a downstream side
thereof is communicated with the micro flow path of the examination
chip at the flow path opening section; a system main body wherein
the micropump unit and the drive fluid tank are integrated and
stored in a storing body; and a mechanism to change a direction of
liquid feeding pressure at the flow path opening section of the
micropump unit in response to detaching and attaching of the
examination chip while carrying out analysis of the analyte in a
state where the examination chip is attached to the system device
main body; wherein the examination chip is connected to the
micropump unit in a way that the flow path opening sections are
overlapped, the micropump feeds the drive fluid to the micro flow
path of the examination chip to push out the reagent to the
downstream side so that the reagent and the analyte are merged and
reacted, and the reaction is detected, whereby a target substance
in the analyte is analyzed.
2. The micro total analysis system of claim 1, wherein all the
micropumps in the micropump unit are connected to a single drive
fluid tank so that the drive fluid stored in the drive fluid tank
is fed through each micropump to the micro flow path of the
examination chip.
3. The micro total analysis system of claim 1, wherein a pressure
opposite to an ejection direction of the micropump is applied at
the flow path opening section of the micropump unit being connected
to the examination chip at least when the examination chip is
detached from the flow path opening section of the micropump
unit.
4. The micro total analysis system of claim 1, wherein the pressure
opposite to the ejection direction of the micropump is applied as a
negative pressure at the flow path opening section of the micropump
unit being connected to the examination chip only when the
examination chip is detached from the flow path opening section of
the micropump unit.
5. The micro total analysis system of claim 4, wherein the negative
pressure is created by lowering a fluid surface of the drive fluid
tank than a connection section to the examination chip.
6. The micro total analysis system of claim 1, wherein the drive
fluid tank can be move up and down.
7. The micro total analysis system of claim 1, wherein the pressure
of the drive fluid at the flow path opening section of the
micropump unit is changed through a negative pressure generation
mechanism attached to a cartridge type drive fluid tank.
8. The micro total analysis system of claim 7, wherein the negative
pressure generation mechanism creates the pressure opposite to the
ejection direction of the micropump through a bias force created by
a restitution force of an elastic substance.
9. The micro total analysis system of claim 4, wherein an absolute
value of the negative pressure is 5 mmAq at a maximum.
10. The micro total analysis system of claim 1, wherein the
micropump comprises; a first flow path, wherein a flow path
resistance varies with a pressure difference, a second flow path,
wherein a change rate of the flow path resistance in respect to a
change of the pressure difference is smaller than that of the first
flow path, a pressure chamber connected to the first flow path and
the second flow path, and an actuator driven by voltage so as to
change an inner pressure of the pressure chamber.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to an micro total analysis
system wherein an analyte and a reagent is mixed to react and a
target substance in the analyte is analyzed using an examination
chip provided with a successive micro flow path to detect the
aforesaid reaction.
PRIOR ART
[0002] In recent years, using micro machine technologies and ultra
micro fabrication technologies, there has been developed a system
where miniaturized devices (for example, a pump, valve, flow path
and sensor) to conventional conduct preparation of the analyte,
chemical analysis, and chemical synthesis are integrated on a chip
(Patent Document 1). The chip so-called .mu.-TAS (Micro Total
Analysis System), Bio Reactor, Lab-On-chip or Bio Chip is expected
to be expanded in application in fields of medical examination and
diagnosis, environmental measuring and agricultural production.
[0003] In each analysis and inspection, quantitative performance of
analysis, accuracy of analysis and economic efficiency in the
examination chip is important. Therefore, it is an object to
establish a fluid feeding system having a high reliability with a
simple structure. A micro fluid control element having a high
accuracy superior in the reliability is desired. Micropump systems
and control methods suitable for the above object have been
suggested by the inventors of the present invention (Patent
Documents 2 to 4).
[0004] When fluid is fed to the micro fluid path of the examination
chip using a pump, if leakage of the fluid occurs in middle-course,
quantitative fluid feeding becomes difficult and smooth fluid
feeding cannot be carried out. A rubber packing is often used for a
connection section between the micropump and the chip. It the
connection section is wet with the fluid, the connection section
thereof tends to cause leakage of the fluid. Thus there is needed a
simple mechanism to avoid such leakage of the fluid.
[0005] On the other hand, in an mage forming apparatus by inkjet
method, there is suggested an apparatus having a negative pressure
adjusting mechanism to keep a distance between an fluid surface of
ink supply reservoir section containing ink in liquid state an ink
ejection port of an inkjet head constant (Patent Document 5). For
adjusting the negative pressure, vertical motion of the ink tank or
biasing by an elastic substance are used. The above mechanism can
maintain stable ejection by compensating fluctuation of the
negative pressure generated by ink consumption.
[0006] [Patent Document 1] Unexamined Japanese Patent Application
Publication No. 2004-28589
[0007] [Patent Document 2] Unexamined Japanese Patent Application
Publication No. 2001-322099
[0008] [Patent Document 3] Unexamined Japanese Patent Application
Publication No. 2004-108285
[0009] [Patent Document 4] Unexamined Japanese Patent Application
Publication No. 2004-270537
[0010] [Patent Document 5] Unexamined Japanese Patent Application
Publication No. 2006-27166
DISCLOSURE OF THE INVENTION
Problems to be Solved by the Invention
[0011] For the analysis using the above micro analysis system,
beside the inspection chip, there is required various kinds of
devices to control liquid feeding in the micro flow path of the
chip, reaction and detection of the reaction thereof, for example,
a micropump, a detection device, and a thermal control device.
Therefore, if leakage of fluid occurs in the devices, a serious
problem is caused not only for analysis but functions of each
device. An object of the present invention is to provide a
mechanism to avoid leakage in fluid feeding securely with a simple
configuration.
Means to Solve the Problems
[0012] A micro total analysis system, having:
[0013] an examination chip provided with a succession of a micro
flow path and a flow path opening section at an upstream side of a
containing position of a reagent in the micro flow path, wherein
the flow path opening section is communicated with a micropump;
[0014] a drive fluid tank to store a drive fluid which pushes the
reagent the upstream side to a downstream side of the micro flow
path of the examination chip;
[0015] a micropump unit provided with a plurality of the micropumps
at each position in a plane direction of a chip, wherein an
upstream side of each micropump is communicated with the drive
fluid tank and at the downstream side thereof, a flow path opening
section communicated with the micro flow path of the examination
chip is provided;
[0016] a system main body wherein the micropump unit and the drive
fluid tank are integrated and stored in a containing body; and
[0017] a mechanism to change a direction of liquid feeding pressure
at the flow path opening section of the micropump unit in response
to detaching and attaching of the examination chip while carrying
out analysis of the analyte in a state where the examination chip
is attached to the system device main body;
wherein after the examination chip is connected to the micropump
unit in a way that the flow path opening sections are overlapped,
the micropump feeds the drive fluid to the micro flow path of the
examination chip to push out the reagent to the downstream side so
that the reagent and the analyte are merged and reacted, and the
reaction is detected, whereby a target substance in the analyte is
analyzed.
[0018] It is preferred that all the micropumps in the micropump
unit are connected to a single drive fluid tank so that the drive
fluid contained in the drive fluid tank is fed through each
micropump to the micro flow path of the examination chip.
[0019] It is characterized in that a pressure opposite to an
ejection direction of the micropump is applied at the flow path
opening section of the micropump unit being connected to the
examination chip at least when the examination chip is detached
from the flow path opening section of the micropump unit.
[0020] It is preferred that the pressure opposite to the ejection
direction of the micropump is applied as a negative pressure at the
flow path opening section of the micropump unit being connected to
the examination chip only when the examination chip is detached
from the flow path opening section of the micropump unit.
[0021] The opposite pressure or the negative pressure can be
created by lowering a fluid surface of the drive fluid tank than a
connection section to the examination chip. This can be realized by
that the drive fluid tank can be moved up and down.
[0022] The direction of the pressure of the drive fluid at the flow
path opening section of the micropump unit can be altered through a
negative pressure generation mechanism attached to a cartridge type
drive fluid tank.
[0023] It is preferred that the negative pressure generation
mechanism creates the pressure through a bias force based on a
restitution force of an elastic substance.
[0024] It is preferred that an absolute value of the above negative
pressure is 5 mmAq at a maximum.
[0025] The micro total analysis system of the present invention
has;
[0026] a first flow path, wherein a flow path resistance varies
with a pressure difference,
[0027] a second flow path, wherein a change rate of the flow path
resistance in respect to a change of the pressure difference is
smaller than that of the first flow path,
[0028] a pressure chamber connected to the first flow path and the
second flow path, and an actuator driven by voltage so as to change
an inner pressure of the pressure chamber.
EFFECTS OF THE INVENTION
[0029] In the micro total analysis system of the present invention,
analysis of a target substance in the analyte is carried out while
the inspection chip is being attached to the system device main
body. Since the micro total analysis system of the present
invention has a mechanism to alter a direction of pressure at a
flow path opening section of the micropump unit in response to
detaching and attaching of the examination chip from the system
device main body, the pump has margin in capacity when fluid is fed
and a consistent fluid feeding is possible, thus occurrence of
fluid leakage at detaching and attaching the chip can be
prevented.
[0030] The mechanism to alter the direction of pressure at flow
path opening section for the purpose of preventing fluid leakage
and a pump mechanism to feed the various kinds of reagents in the
micro flow path of the inspection chip to downstream side have
simple and compact configurations.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIG. 1 is a system schematic diagram showing a configuration
of the micro total analysis system of the present invention.
[0032] FIG. 2 is a perspective view showing an embodiment of the
micro total analysis system of the present invention.
[0033] FIG. 3 is a view showing internal configuration of the
system main body of the micro total analysis system in FIG. 2.
[0034] FIG. 4 is a perspective view showing an example of a
plurality of the micropumps and the flow path arrangement of the
chip connection section communicating to the pumps thereof in an
embodiment of the micro total analysis system of the present
invention.
[0035] FIG. 5 (a) shows a conventional method wherein a position of
the drive fluid tank stored in the system device main body is
fixed.
[0036] FIG. 5 (b) shows another conventional method wherein a
position of the drive fluid tank stored in the system device main
body is fixed.
[0037] FIGS. 6 (a) to (c) show methods to eliminate a water head
difference when the examination chip is detached from the system
device main body due to hoisting motion of the drive fluid
tank.
[0038] FIGS. 7(a) to (c) are methods where negative pressure
generating mechanism utilizing pressure of elastic substance
(sponge or spring).
[0039] FIG. 8 is a plane view of the examination chip in an
embodiment of the micro total analysis system of the present
invention.
[0040] FIG. 9 is a cross-sectional view of a fluid feeding control
section (water repellant valve).
[0041] FIG. 10 is a cross-section view of the micropump unit in
FIG. 4.
DESCRIPTION OF SYMBOLS
[0042] 1 Micro total analysis system [0043] 2 Examination chip
[0044] 3 System device main body [0045] 11 Micropump unit [0046] 12
Micropump [0047] 12a to 12i Micropump [0048] 13 Chip connection
section [0049] 14 Opening [0050] 15 Opening [0051] 15a to 15c
Opening [0052] 16a and 16b Through hole [0053] 17 Substrate [0054]
18 Substrate [0055] 19 Substrate [0056] 20 Flow path [0057] 20a to
20C Flow path [0058] 21 Piezoelectric element [0059] 22 Pressure
chamber [0060] 23 First flow path [0061] 24 Second flow path [0062]
25 First fluid chamber [0063] 26 Second fluid chamber [0064] 31
Pump connection section [0065] 32a to 32j Opening [0066] 33a to 33c
reagent containing section [0067] 34a and 34b end section [0068] 35
Merging section [0069] 36 Reagent mixing section [0070] 37 Analyte
containing section [0071] 38 Merging section [0072] 39 Reacting
section [0073] 40 Detection section [0074] 51 Fluid feeding control
section (water repellent valve) [0075] 52 Fluid feeding control
path [0076] 53a and 53b Flow path [0077] 54 Fluid [0078] 61 Drive
fluid tank [0079] 62 Containing body [0080] 63 Chip inserting port
[0081] 64 Display section [0082] 65 Conveyance tray [0083] 66
Peltiert element [0084] 67 Heater [0085] 68 Light source [0086] 69
Detection device
PREFERABLE EMBODIMENT OF THE INVENTION
[0087] FIG. 1 shows an embodiment of the micro total analysis
system of the present invention, having
[0088] an examination chip 2 provided with a succession of a micro
flow path and a flow path opening section to communicate with a
micro pump 11 at an upstream side of a containing position of a
reagent in the micro flow path;
[0089] a drive fluid tank 61 to contain a drive fluid which pushes
the reagent from the upstream side to a downstream side of the
micro flow path of the examination chip 2;
[0090] a micropump unit 11 provided with a plurality of the
micropumps 12 at each position in a surface direction of one
examination chip 2, wherein an upstream side of each micropump 12
is communicated with the drive fluid tank 61 and at the downstream
side thereof, a flow path opening section communicating with the
micro flow path of the examination chip 2 is provided;
[0091] a system main body 3 (not illustrated in FIG. 1) wherein the
micropump unit 11 and the drive fluid tank 61 are integrated and
stored in a storing body; and
[0092] a mechanism to change a direction of liquid feeding pressure
at the flow path opening section of the micropump unit 11 in
response to detaching and attaching of the examination chip 2 while
carrying out analysis of the analyte in a state where the
examination chip 2 is attached to the system device main body
3;
[0093] wherein after the examination chip 2 is connected to the
micropump unit 11 in a way that the flow path opening sections are
overlapped, the micropump 12 feeds the drive fluid to the micro
flow path of the examination chip 2 to push out the reagent to the
downstream side so that the reagent and the analyte are merged and
reacted, and the reaction thereof is detected, whereby a target
substance in the analyte is analyzed.
[0094] Further, the system device main body 3 is preferred to be
provide with a detection section 69 to detect the reaction in the
examination chip 2, a LED control section 119 to control a light
emitting section 120 to radiate light onto the examination chip 2,
a valve control section 118 to control a vale of the examination
chip 2, a heater temperature control section 117 to control
temperature of the examination chip 2, a peltiert temperature
control section 114, a tray loading mechanism 115, a residual
quantity measuring section 131, a pump drive section 130 to drive
the micropumps 12, and a control device 110 to control the sections
thereof provided in the storing body (FIG. 1). Also, it is
preferred to provide a data processing section 111 to process data,
a display section 112 to display a result of the data processing,
and an input/output section 113 to communicate with outside.
<Macro Total Analysis System>
[0095] To process a large number of analytes, a method wherein
reaction and analysis are carried out by attaching the examination
chip to a separate system device main body is preferred. In the
present embodiment, the micro total analysis system 1 is configured
with the system main body and the examination chip 2 (FIG. 1). FIG.
2 is a perspective view showing an example of the micro total
analysis system 1. FIG. 3 shows an internal structure of the system
main body of the micro total analysis system 1. The micro total
analysis system 1 will be described with reference to both drawings
thereof. The system device main body 3 is provided with a storing
body 62 in a shape of a housing to store each device for analysis.
Inside the storing body 62, a chip connection section 13 having a
flow path opening to communicate with the examination chip 2 and a
micropump unit 11 having a plurality of micropumps (not illustrated
in FIG. 2) are provided.
[0096] Further, inside the storing body 62, a detecting processing
device (detection device 69, such as a LED light source 68, a
photoelectron magnification tube and a CCD camera to carry out
optical detection), and a control device (unillustrated) to control
the detection processing device and the micropump unit 11 are
provided. Besides, control of fluid feeding through the micropump
and control of the detection processing device to detect the
reaction in the examination chip 2, the control device carries out,
temperature control of the examination chip 2 through a
heating/cooling unit, control of reaction in the examination chip
2, collection (measuring) and processing of the data. The micropump
is controlled by applying a drive voltage to the micropump
according to a program in which various conditions related to an
order of fluid feeding, a flow amount and timing are set.
[0097] In the micro total analysis system 1, after the examination
chip 2 is set inside the storing body 62 in a state where a pump
connection section 31, configured with a flow path opening provided
at an upstream side (for example, an upstream side of the reagent
containing section and an analyte containing section) in the micro
flow path of the examination chip 2, and a chip surface in the
vicinity of the flow path opening thereof, is adhered onto a chip
connection section 13 of the micropump unit 11 firmly in a
fluid-tight state, the target substance in the analyte is analyzed
in the examination chip 2. The examination chip 2 is placed on a
conveyance tray 65 and entered inside the storing body 62 through a
chip insertion opening 63. However, if the examination chip 2 can
be set inside the storing body 62 in a state where the examination
chip 2 is pressed onto the micropump unit 11, the conveyance tray
is not always necessary to be used.
[0098] Inside the storing body 62, the heating/cooling unit
(peltiert element 66 and heater 67) to partially heat and cool the
examination chip 2 is provided at a predetermined position. For
example, by adhering the peltiert element onto an area of reagent
containing section in the examination chip 2 through crimping, the
reagent containing section is selectively cooled. Whereby
deterioration of the reagent is prevented, and by adhering the
heater 67 onto an area of the flow path configuring the reaction
section though crimping, the reaction section is selectively
heated, whereby the reaction section is adjusted at an appropriate
temperature for reaction.
[0099] The micropump unit 11 is connected to one drive fluid tank
61 and the upstream side of each micropump is communicated with the
drive fluid tank 61. On the other hand, the downstream side of each
micropump is communicated with the flow pass opening provided on
one side of the micropump unit 11. The examination chip 2 is
connected to the micropump unit 11 in a way that the flow path
opening of the each chip communicating with each micropump is
connected with each flow path opening provided at the pump
connection section 31 of the examination chip 2.
[0100] The micropump feeds an oil base drive fluid such as mineral
oil or a water based drive fluid contained in the drive fluid tank
61 to a containing section of each fluid in the examination chip 2
though the chip connection section 13, and pushes the fluid in each
containing section to the downstream side with the drive fluid so
as to feed the liquid.
[0101] A series of analysis process including prior processing,
reaction and detection, is carried out in a state where the
examination chip 2 is attached to the system main body 1 in which
the micropump, the detection processing device and the control
device are integrated. Preferably, feeding of the reagent and
analyte, prior processing, specific reaction and optical
measurement based on mixture are carried out automatically as a
succession of consecutive process, and measurement data is stored
in a file along with necessary conditions and recording items. In
FIG. 2, a result of the analysis is displayed on the display
section 64 of the storing body 62.
<Drive Mechanism of Fluid in the Flow Path>
[0102] In the analysis system of the present invention, all the
micropumps 12 in the micropump units 11 are communicated to the
drive fluid tank 61, and the fluid contained in the drive fluid
tank 61 is fed to the micro flow path of the examination chip 2
through each micropump 12. The drive fluid is used to feed the
regent and the analyte into the micro flow path of the examination
chip and to convey the regent and analyte to the specific reaction
section and the detection section, as well as to lead the above
fluid to the examination chip 2. As above, in order to feed each
reagent, all the micropumps 12 are provided for one examination
chip 2, and at analysis, the chip connection section 13 (opening
section) of the micropump 12 and the pump connection section 31
(opening section) of the examination chip 2 are overlapped so that
the flow paths on both sides communicate each other, thus the pump
mechanism to push the regent in the micro flow path of the
examination chip 2 to downstream side can be simplified and
compact.
[0103] Further, since the plurality of the micropumps commonly use
the single drive fluid tank, special piping to connect the drive
fluid tank 61 with micropump unit 11 in a shape of a chip or a chip
for connection is not necessary. Therefore the pump mechanism to
push the regent in the micro flow path of the examination chip 2 to
downstream side can be simplified and compact.
[0104] It is necessary to firmly connect the connection section
between the micropump 12 and the examination chip 2 so as to
prevent the fluid leakage. In particular, if the connection section
is in a wet condition with the fluid, leakage of the fluid tends to
occur when the chip is connected. In the micro chips for analysis,
the connection section is usually configured with a rubber packing.
Thus if the micropump and the examination chip are connected while
such connection sections are wet with the fluid, fluid leakage
tends to occur. Thus it has been necessary to prevent the
connection sections from being wet so that the fluid leakage does
not occur from the connection sections between the micropump and
the examination chip.
[0105] As a mechanism to prevent such fluid leakage, there is
preferred a simple and secure mechanism to alter a direction of the
pressure at the flow path opening section of the micropump unit in
response to detaching and attaching of the examination chip from
the system device main body. Namely, at the flow path opening
section of the chip connection section 13 on the micropump unit to
be connected with the examination chip, a pressure having opposite
direction to the ejection direction of the micropump is applied at
least when the examination chip is detached from the opening
section (chip connection section 13) of the micropump unit so that
occurrence of fluid leakage from the connection section between the
micropump unit and the examination chip is prevented. The pressure
having opposite direction is about 5 mmAg (or 5 mmH.sub.2O)
depending on the pump and size of the ejection port.
[0106] The above mechanism is realized by cooperation of the
analysis system device main boy and the drive fluid tank of the
present invention. As the mechanisms, the present invention
suggests a method to change the position of the drive fluid tank
and a method to adding a negative pressure generation mechanism to
the drive fluid tank. In the both methods, it is necessary to apply
the pressure having opposite direction to the ejection direction of
the micropump at the flow path opening section of the micropump
unit being connected to the chip, at least when the examination
chip is detached from the opening section of the micropump unit.
This is because, when more than two examination chips are
subsequently connected to the same system device main body to carry
out analysis subsequently (in particular, when a large number of
analyte are to be processed), it is necessary to prevent the
opening section of the micropump to be connected to the examination
chip from being wet with the fluid leaked. The problem caused by
leakage is described in the forgoing.
Conventional Exemplary Embodiment
[0107] A configuration in FIG. 5 utilizes a conventional drive
fluid feeding method. FIG. 5 (a) is a cross-sectional view showing
a state where the micropump 12 feeds the drive fluid to the
examination chip 2, and FIG. 5(b) is a cross-sectional view showing
a state where the examination chip 2 is detached from the micropump
12. As FIG. 5 (a) shows, the flow path 53 of the examination chip 2
is connected to the opening section on an ejection side of the
micropump 12 via a rubber packing 91. Also, by locating the
examination chip 2, preferably the drive fluid tank, at a position
rather higher than the micropump unit, a faint pressure caused by
gravity is applied to the micropump unit in the feeding direction
thereof so as to realize smooth fluid feeding through the fluid
feeding pump. However, as the arrow in FIG. 5 (b) shows, since the
fluid surface of the drive fluid tank is at the higher position by
Y.phi. than the position of the chip connection section 95 of the
rubber packing 91, the drive fluid always tends to leak out by a
water head pressure (a pressure based on height difference between
both fluid surfaces) when the fluid feeding pump stops. Thus as
FIG. 5 (b) shows, when the examination chip is detached, the drive
fluid flows out from the micropump through the connection section
by a pressure caused by gravity and spills on the chip connection
section 95. Therefore, in the conventional drive fluid feeding
method shown by FIG. 5, the drive fluid always tends to flow out
when the examination chip is not connected, unless a prevention
measure is taken.
Drive Fluid Tank Hoisting Method
[0108] FIG. 6 is explanatory diagrams to explain a configuration of
an embodiment of the present invention utilizing drive fluid
feeding method. FIG. 6(a) and FIG. 6(b) are cross-sectional view
showing a state where the examination chip 2 is detached from the
micropump 12. While the examination chip 12 is detached from the
opening section of the micropump unit 11 and the micropump is not
operating, if the fluid surface of the drive fluid tank is in a
position to apply a pressure of +5 mmAq a at maximum in the
ejection direction at the chip connection opening of the micropump
unit 11, fluid leakage is not likely to occur. Because of the water
repellent characteristic of the rubber packing 91 at the opening
section of the connection section, the fluid does not soakingly
flow out. For example, as FIG. 6 (a) shows, if the position of the
fluid surface in the drive fluid tank 61 is lower than the position
of the chip connection section 95 by Y1 as the arrow in the FIG.
6(a) shows, the fluid surface of the drive fluid is at lower
position than that of the chip connection section 95, thus the
water head pressure becomes zero or negative. In this case, the
drive fluid flows in an opposite direction to the ejection
direction and the drive fluid does not flow out.
[0109] FIG. 6 (b) shows an example where the drive fluid tank 61 is
moved up and down direction through a driving mechanism. In the
figure, A denotes the fluid surface in the drive fluid tank 61
while the examination chip 2 is connected, and B denotes the fluid
surface in the drive fluid tank 61 while the examination chip 2 is
disconnected. As explained in FIG. 6 (a), the fluid surface in the
fluid drive tank 61 while the examination chip 2 is disconnected is
in the position lower than that of the chip connection section 95
by Y1. When the examination chip 2 is connected, the drive fluid
tank 61 is ascended through the unillustrated drive mechanism so as
to bring the fluid surface in the drive fluid tank 61 to a position
of A. Thus, contrarily, the position of the fluid surface in the
drive fluid tank 61 becomes higher than the position of the chip
connection section 95 by Y2, therefore a pressure in the ejection
direction of the micropump 12 can be applied.
[0110] In the above embodiment, the drive fluid tank 61 can be
moved up and down direction so as to change the fluid surface of
the drive fluid appropriately. A motor is used to realize the
movement so that the height of the fluid surface can be adjusted
appropriately. A position of the fluid surface when the drive fluid
tank is lowered and stopped is set in a range where a pressure of
+5 mmAg to -5 mmAg is generated. Thus a lower position of the drive
fluid tank is also determined to satisfy such pressure rang. If the
pressure is greater than +5 mmAg, there is a danger that the drive
fluid leaks out from the chip connection opening section of the
micropump. Also, if the pressure is smaller than -5 mmAg, a
back-flow of the drive fluid occurs and there is a danger that air
babbles go into the flow path and the pump inside. In practice,
considering the fluctuation of the fluid surface in the drive fluid
tank due to the use of the drive fluid, the position of the drive
fluid tank can be determined based on data from a fluid surface
sensor, a measurement of weight of the drive fluid tank, and a
result of calculation of fluid consumption on the basis of number
of ejection. Or the position of the drive fluid tank can be set at
a predetermined position at which the negative pressure is always
generated.
[0111] As above, in case the drive fluid tank 61 can be moved up
and down direction, while the examination chip 2 is connected, the
fluid surface is risen to assist the fluid feed through the
micropump and when the examination chip 2 is disconnected, the
fluid surface is lowered so that the negative pressure is
preferably generated to enable prevention of the drive fluid from
moving in the ejection direction of the micropump. Incidentally, a
fluctuation of the water head pressure caused by descending of the
fluid surface in the drive fluid tank due to consumption of the
drive fluid falls within the above pressure range or within a
fluctuation of the ejection pressure of the micropump.
[0112] FIG. 6 (c) is a cross-sectional view showing an example of
integration of the micropump and the drive fluid tank 61. In this
case, there can be an embodiment where the drive fluid tank is
lowered to a predetermined position through a mechanical operation
in relation to pump halt and detaching of the examination chip
2.
[0113] Incidentally, as another embodiment where the drive fluid
tank is relatively moved up and down direction, the micropump unit
can be hoisted to relatively eliminate the water head
difference.
[0114] According to the above mechanism, at fluid feeding, a
capacity margin of the micropump is created and consistent fluid
feeding becomes possible. Thus occurrence of fluid leakage at
detaching the examination chip can be prevented. Method wherein a
negative pressure generation mechanism is provided at the drive
fluid tank
[0115] Alteration of the pressure direction at the flow path
opening section on the chip connection side of the micropump unit
can be realized through a negative pressure generation mechanism
instead of hoisting the drive fluid tank. As FIG. 7 is structural
diagram of an example of a negative pressure generation mechanism
added to the drive fluid tank 61. As FIG. 7 shows the negative
pressure generation mechanism added to the cartridge type drive
fluid tank 61 is preferable. In the method, an embodiment where the
micropump and the drive fluid tank are integrated is also
preferable. The pressure having the opposite direction to fluid
feeding or pump ejection direction can be applied in the flow pass
which communicates the micropump and the drive fluid tank, by
generating a negative pressure through a negative pressure
generation mechanism which is added to the drive fluid tank, but
not by positional change of the fluid surface in the drive fluid
tank.
[0116] As the negative pressure generation mechanism, an embodiment
where the negative pressure is generated by a bias force of an
elastic substance which tends to return an original position is
considered. As the elastic substance provided in the drive fluid
tank 61, various things such as a coil spring 204, a leaf spring
203 and a sponge 200 can be used. Specifically, as FIG. 7 (a)
shows, an embodiment where a sponge 200 is stuffed in the drive
fluid tank 61 (the negative pressure is generated by a force of the
sponge 200 to absorb the drive fluid), or an embodiment where an
inner cartridge gab 201 in which the drive fluid is contained is
pulled by a force of the spring (in the figure, the coil spring 204
or the leaf spring 203) are devised. As above, as far as the
negative pressure is generated by the bias force of the elastic
substance, kinds and shapes of the elastic substance are no object.
In the above method, the mechanism is simple without using
electrical power source such as a motor. Therefore, a simple, power
saving and low cost device main boy can be realized.
[0117] As the drive fluid is fed from the drive fluid tank 61, a
position of the elastic substance is changed in accordance with the
reducing of fluid amount, thereby a potential force of restitution
to return the elastic substance to an original position is
generated. When moving of the drive fluid is stopped, based on the
bias of the restitution force of the elastic substance, a force
having a direction opposite to the previous direction is applied
and the negative pressure is generated.
[0118] So far, the embodiment in which the negative pressure
generation mechanism is added to the cartridge type drive fluid
tank has been described. Since the drive fluid tank is a cartridge
type, detaching of the tank thereof is easy. Also, the negative
pressure generation mechanism is not limited to the embodiment in
the forgoing. Meanwhile, the cartridge type drive fluid tanks can
be connected respectively to individual micropumps.
[0119] The negative pressure to be generated conforms with that of
the tank hoisting method thus a negative pressure of up to -5 mmAg
is preferable to be generated. In the same manner, the position of
displacement of the elastic substance is determined so as to
generate the above negative pressure based on data such as the
result of calculating the drive fluid consumption amount on the
basis of number of ejection time.
[0120] By adding the above negative pressure generating mechanism
to the drive fluid tank 61, a marginal capacity is created to the
micropump when feeding the fluid, and consistent fluid feeding
becomes possible. Further, leakage of liquid at detaching the
examination chip 2 does not occur.
<Examination Chip>
[0121] In the examination chip 2 used in the present embodiment,
each flow path element and structural sections are allocated
functionally in appropriate positions with a microfabricating
technology so that the examination chip 2 is used as a micro
reactor in chemical analysis, various examinations, and
processing/separating of the analyte.
[0122] On the examination chip 2, a plurality of reagent containing
sections to contain various the reagents are provided, in which
reagents, washing liquid and denaturation process liquid used for a
specific reaction are contained, because reagents are preferred to
be contained in advance to hasten the examination at any time and
place.
[0123] The examination chip 2, for example, can be configured with
a groove forming substrate in which a groove is formed on the
substrate surface to form a flow path, and a covering substrate
which is adhered onto the groove forming substrate thereof. On the
groove forming substrate, each structure section and a flow path
communicating with the structure section are formed. As an specific
example of such structure, there is cited a fluid feeding control
section such as each containing section (reagent containing section
and analyte containing section), a fluid reservoir such as a waste
fluid reserving section, a valve base section, fluid feeding
control section (a water repellent valve indicated in FIG. 9 to be
described later), a reverse flow preventing valve (check vale and
active valve), a reagent quantitative determination section, mixing
section, and reaction section and detection section. Such
structural sections and flow path can be formed on the covering
substrate. By adhering the covering substrate onto the groove
forming substrate to cover the above structural sections and flow
paths, the examination chip is formed. Meanwhile, to optically
detect the reaction in the examination chip, an optical
transparency covering substrate has to be adhered so that at least
the detection section within the above structural sections is
covered by the optical transparency covering substrate thereof.
Also, more than three substrates can be laminated to form the
examination chip 2.
[0124] The examination chip 2 is usually formed by combining more
than one forming material appropriately. As the forming material of
the examination chip 2, for example, plastic resin, various kinds
of inorganic glasses, silicon, ceramic and metal are cited.
[0125] Among them, for the examination chip intended for a large
number of analytes, particularly a clinical analyte having a risk
of influence or exposure, disposability is desired. Further, from a
view point that to provide capability of various applications and
mass productivity is preferred, use of the plastic resin for the
forming material of the examination chip is preferred.
[0126] For the substrate such as groove forming substrate on which
the flow path is formed, there is preferred a plastic having a
repellent character and hydrophobic character wherein distortion of
the flow path due to absorption of the fluid is not likely to
occur, thus a small amount of analyte fluid can be fed without any
loss. For such material, resins such as polystyrene, polyethylene,
polypropylene, polyethylene terephthalate, polyethylene
naphthalate, polyethylene vinyl alcohol, polycarbonate,
polymethylpentene, fluorocarbon, saturated cyclic polyolefin are
cited. In case heating at around 100.degree. C. is required by the
analysis, resins superior in heat resistance, for example,
polycarbonate, polyimide, polyetherimide polybenzimidazole,
polyether ketone are used for the material of the substrate.
[0127] The flow path of the examination chip 2, as the micro
reactor, is formed on the substrate in accordance with a flow path
arrangement designed in advance to suit purposes. The flow path in
which the fluid flows is a micro flow path having a width in micro
meter order, i.e. a width of several tens to several hundreds
.mu.m, preferably 50 to 200 .mu.m, and a depth of 25 to 300 .mu.m,
preferably 50 to 100 .mu.m. As the width of the flow path becomes
narrow, the flow path resistance increases, thus a problem of fluid
feeding may occur. If the width of the flow path is too wide, an
advantage of micro scale space is spoiled. An over all lateral and
longitudinal size of examination chip 2 is typically several tens
mm and the height is several mms.
[0128] Each structural section and the flow path of the substrate
can be formed through a conventional microfabricating technology.
Typically, transfer of micro structure through photo lithography
technology using photoconductive resin is preferable. By utilizing
the transfer structure thereof, removing of unnecessary portions,
adding of necessary portions, and transferring of shapes are
carried out. For example, a pattern to form the structural element
of the examination chip is formed by the photo lithography
technology, and the pattern thereof is formed on a resin through
transfer. As a basic material of the substrate on which the micro
flow path of the micro reactor is formed, plastic resins superior
in mechanical characteristics where structures in sub micron order
can be accurately transferred is preferably used. In particular
polystyrene and polydimethylsiloxane are superior in
characteristics of shape transfer. Each structural section and the
flow path on the substrate can be formed through injection molding
and extrusion molding where needed.
[0129] At an upstream side in the micro flow path of the
examination chip, for example, at an upstream side of the
containing section to contain each fluid such as, reagent and
analyte, a pump connection section to connect other micropump is
provided. At the pump connection section, a flow path opening
section communicating with the aforesaid containing section is
provided, and the drive fluid is supplied from the micropump
through the flow path opening, thus fluid in each containing
section is pushed to the downstream side. Flow of the fluid through
such flow path will be described in FIG. 8 specifically. FIG. 8 is
a plane view of an examination chip in an embodiment of the micro
total analysis system of the present invention. In the examination
chip 2, three reagents are contained in a total of three flow paths
i.e. the reagent containing sections 33a, 33b and 33c. At both ends
of the reagent containing sections (in the reagent containing
section 33a, an end section 34a at an upper stream side and an end
section 34b at a downstream side) the fluid feeding control section
(water repellent valve) having the structure shown by FIG. 9 is
provided. The reagent is encapsulated in the flow path between the
water repellent valves.
[0130] FIG. 9 is a cross-sectional view of the fluid feeding
control section (water repellent valve). The fluid feeding control
section 51 is provided with a fluid feeding control path 52. A
cross-sectional area (a cross-sectional area vertical to the flow
path) of the fluid feeding control path 52 is smaller than the
cross sectional areas of a flow path 53a at an upstream side and
flow path 53b at a downstream side.
[0131] If the flow path wall is formed with a hydrophobic material
such as a plastic resin, a fluid 54 in contact with fluid feeding
control path 52 is restricted by a difference of the surface
tensions between the flow path walls to pass through towards the
flow path 53b at the downstream side.
[0132] To flow out the fluid 54 to the flow path 53b at the
downstream side, the micropump applies a fluid feeding pressure
which is more than a predetermined pressure, whereby the fluid 54
is pushed from the fluid control path 52 to the fluid path 53b at
the downstream side against the surface tension. After the fluid 54
flows out to the flow path 53b, the fluid flows to the flow path
53b at downstream side without maintaining the fluid feeding
pressure required to push out a front end of the fluid 54 to the
flow path at the downstream side. Namely, Passing of the fluid
through the fluid feeding control path 52 is interrupted until the
fluid feeding pressure in the positive direction from an upstream
side to a downstream side reaches to a predetermined pressure, and
when the fluid feeding pressure more than the predetermined
pressure is applied, the fluid 54 passes through the fluid feeding
control path 52.
[0133] Incidentally, though the specific description is omitted, in
the micro flow path of the examination chip 2, in FIG. 8, the fluid
feeding control sections 51 in FIG. 9 are provided other than at
the positions of the both ends of the reagent containing sections
33a to 33c. For example, the fluid feeding control sections is
provided at an end section at a merging section 38 side of the
reagent mixing section 36 and the analyte containing section 37 to
control timing to start fluid feeding to the flow path onward.
[0134] At an upstream side of the reagent containing sections 33a
to 33c in FIG. 8, openings 32c to 32e to open one surface of the
chip 2 to outside are provided. The openings 32c to 32e are matched
with the flow path openings provided on a connection surface (chip
connection section) of the micropump unit to be communicated with
the micropumps, when the examination chip 2 is overlapped and
connected with the chip connection section of the micropump unit
described later.
[0135] Meanwhile, the openings 32a, 32b and 32f to 32j are also
communicated with the micropumps by connecting the examination chip
2 with the chip connection section of the micropump unit. The pump
connection section 31 is configured with a surface including the
openings 32 a to 32j, and by adhering the pump connection section
31 with the connection surface (chip connection section) of the
micropump unit, the examination chip 2 and the micropump unit 11
are connected. In the pump connection section 31, it is preferred
that an adhering surface is formed with flexible resins (having
elasticity and shape subserviency characteristic) such as
polytetrafluoroethylene and silicone resins, so as to prevent
leakage of the drive fluid by ensuring a necessary packing
performance. Such adhering surface having a flexibility can be
realized by the substrate itself configuring the examination chip,
or by a separate material having flexibility adhered on a vicinity
of the flow path opening on the pump connection section.
[0136] The reagents contained in the flow paths 33a to 33c flow
into the merging section 35 passing through the fluid feeding
control section 51 of FIG. 9 with individual micropumps
communicating to the openings 32c to 32e so as to be with mixed
three kinds of reagents at reagent mixing section 36 representing a
successive flow pass.
[0137] The mixed reagent 36 mixed in the reagent mixing section 36
is merged with an analyte stored in the analyte containing section
37 at merging section 38. Incidentally, the mixed reagent is pushed
out to the downstream side with the drive fluid through the
micropump communicating to the opening 32b, and the analyte is
pushed out to the downstream side with the drive fluid through the
micropump communicating to the opening 32a. A mixed fluid of the
mixed reagent and the analyte is contained in a reaction section 39
and reaction starts by heating.
[0138] The fluid after reaction is fed to a detection section 40,
and a target substance is detected through an optical detection
method. Meanwhile, the individual pumps respectively communicating
to the openings 32f to 32j push out respective reagents (for
example, fluid to cease reaction of mixed reagent and analyte,
fluid to carried out a necessary process such as labeling the
target substance of analysis, and washing fluid) contained in
advance in the flow paths after the openings at predetermined
timing to downstream side.
<Micropump Unit>
[0139] FIG. 4 is a perspective view of the micropump unit in an
embodiment of the micro total analysis system of the present
invention, and FIG. 10 is a cross-sectional view of the view
thereof. The micropump unit 11 is preferably configured with a
substrate 17 formed with silicon, a substrate 18 formed with glass
thereon and a substrate 19 formed with glass thereon. The
substrates 17, 18 and 19 are bonded with anodic bonding, direct
bonding or an adhesive. Meanwhile, the materials of the substrates
are only exemplary materials.
[0140] The micropump 12 (piezoelectric pump) is configured with an
inner space between the substrate 17 formed with silicon and the
substrate 18 formed with glass bonded through the anodic bonding
thereon.
[0141] The substrate 17 is a silicon wafer on which a predetermined
shape is formed by lithography technology. There are formed a
pressure chamber 22, a first flow path 23, a first fluid chamber
25, a second flow path 24, and a second fluid chamber 26, through
microfabrication including, for example, forming of an oxide film
on the silicon substrate surface, application of registration,
exposure and development of the registration, etching of the oxide
film, and etching of silicon through IPC (inductively Coupled
Plasma).
[0142] At a position of the pressure chamber 22, the silicon
substrate is formed into a diaphragm, and a piezoelectric element
21 formed with titanic acid lead zirconate (PZT) ceramic is adhered
thereon,
[0143] The micropump is driven by a control voltage applied to the
piezoelectric element 21 as follow. The piezoelectric element 21
vibrates with an applied voltage having a predetermined wave shape
and the silicon diaphragm at the position of the pressure chamber
22 vibrates, whereby a volume of the pressure chamber 22 increases
and decreases. The first flow path 23 and the second flow path 24
are the same in width and depth, and the second flow path is longer
than the first flow path in length. In the first flow path 23, as
the pressure difference increases, turbulent flow which flows
whirls is generated to increase flow path resistance. On the other
hand, in the second flow path, because of long flow path, a laminar
flow tends to occur even if the pressure difference increases. Thus
a change rate of the flow path resistance in respect to change of
the pressure difference is small compared to the first flow path
23.
[0144] For example, by adjusting the control voltage applied to the
piezoelectric element 21, the volume of the pressure chamber 22 is
reduced while giving a large pressure difference by quickly
displacing the silicon diaphragm in a direction towards the inside
of the pressure chamber 22, then the volume of the pressure chamber
22 is increased while giving a small pressure difference by slowly
displacing the silicon diaphragm in a direction towards the outside
of the pressure chamber 22, whereby the drive fluid is fed from the
right to the left in FIG. 10 in a negative direction.
[0145] Contrary to the above, the volume of the pressure chamber 22
is increased while giving a large pressure difference by quickly
displacing the silicon diaphragm in a direction towards the outside
of the pressure chamber 22, then the volume of the pressure chamber
22 is reduced while giving a small pressure difference by slowly
displacing the silicon diaphragm in a direction towards the inside
of the pressure chamber 22, whereby the drive fluid is fed from the
left to the right in the figure thereof in a positive
direction.
[0146] Meanwhile, a difference of the change rate of the flow path
resistance in respect to change of the pressure difference in the
first flow path 23 and the second flow path 24 is not always
necessary to be caused by the difference of the length of the flow
path, and may caused by a difference in shapes.
[0147] Flow amount control through the micropump 12 is realized by
adjusting a voltage applied to the piezoelectric element 21. A
maximum voltage applied to the piezoelectric element is about
several volts to several tens of a volt and 100 volt at a maximum.
The cycle of the drive voltage is about 11 KHz.
[0148] Two electrodes to drive the piezoelectric element 21 are
connected with flexible wires. One electrode of the piezoelectric
element 21 is connected with a gold electrode electrically by
forming a gold electrode on a surface of the silicon diaphragm and
by bonding one surface of the piezoelectric element 21 onto the
gold electrode with an adhesive, and the gold electrode thereof and
the flexible wire are connected. Also, gold plating is applied on
the other surface of the piezoelectric element 21, and the flexible
wire is directly connected to the gold plated portion thereof.
[0149] Meanwhile, other substrate than the silicon substrate can be
used as the substrate to form the micropump 12, for example, a
photoconductive glass.
[0150] Also, as the micropump, other than the piezoelectric pump,
for example, a check valve type pump can be formed. In the present
embodiment a piezoelectric pump is preferably used.
[0151] As the glass substrates 18 and 19 which are laminated on the
silicon substrate 17, for example, Pyrex.TM. glass (Pyrex is a
trade mark of Corning Glass Works) and Tempax.TM. glass (Tempax is
a trade mark of Schott Glasswerk) can be used.
[0152] In FIG. 10, the micropump 20 supplies the drive fluid from
the opening 15, through the flow path 20. On the substrate 19, the
flow path 20 is patterned. As an example, a shape and dimensions of
the flow path 20 are that a cross section is rectangular, a width
is about 150 .mu.m and a depth is about 300 .mu.m. At a downstream
side of the flow path 20, there is provide an opening 15 to
communicate the micropump 20 with the micro flow path of the
examination chip by positioning the opening 15 with the openings
32a to 32k of the pump connection section in the examination chip
in FIG. 8. The opening 15 of the chip connection section can be
formed larger than the width of the flow path 20 where needed so
that positioning of the opening of the examination chip with the
opening 15 of the chip connection section can be carried out
appropriately. As FIG. 4 shows, since the drive fluid can be
ejected from the opening 15 provided at a desired position on the
chip surface of the micropump unit 11, a leading flow path to feed
the drive fluid to a discretionary position can be omitted or
reduced.
[0153] An upstream side of the flow path 20 is communicated with
the micropump 20 via a through hole 16b on the substrate 18,
through a flow path provided on the substrate 17. Also, the
upstream side of the micropump 12 is communicated with an opening
14 provided on the glass substrate 19 via a through hole 16a of the
substrate 18, through a flow path provided on the substrate 17. The
opening 14 is connected to an unillustrated drive fluid tank. The
opening 14 is connected via a silicone resin packing.
[0154] Meanwhile, the micropump unit thereof is merely an example
and various kinds of micropump unit on which a connection openings
to communicate with the micropump, flow path, examination chip and
drive fluid tank are formed can be formed by photolithography
technology. For example, there can be configured a micropump unit
where a silicon substrate on which a structure of the micropump is
formed through etching, a glass substrate is laminated on the
photoconductive glass substrate, PDMS is further laminated thereon,
and further more a substrate formed with a plastic resin, glass,
silicon or ceramic on which a flow path groove and a connection
opening are formed is laminated thereon.
[0155] In the embodiment in FIG. 4, a piezoelectric pump is used as
the micropump. The openings 15a, 15b and 15c are respectively
communicated with the openings 32c, 32d and 32e of the examination
chip in FIG. 8. The micropump 12 feeds the drive fluid through the
flow path 20, the opening 15 and opening 32 and pushes the reagent
contained in the reagent containing section 33 to the downstream
side.
<Analyte and Target Substance>
[0156] The micro total analysis system of the present invention can
be preferably applied to examination of which target substance is
various biological substances such as gene and nucleic acid. The
examination chip for the biological substance other than the gene
such as protein, enzyme has a substantially the same configuration.
Usually, the reagents and buffer solutions (used for dilution and
washing) have only to be changed. In the case thereof, allocation
and number of the fluid feeding element may be changed. One skilled
in the art can change kind of analysis readily by providing
necessary elements on the examination chip, for example, for
immunoassay method and applying slight modification including
change of the flow path and specifications.
[0157] As above while the embodiments of the present invention have
been described, the present invention is not limited to the
embodiments thereof and changes and variations may be made without
departing from the spirit of the invention.
* * * * *