U.S. patent application number 12/149822 was filed with the patent office on 2008-10-02 for microchemical chip.
This patent application is currently assigned to NGK INSULATORS, LTD.. Invention is credited to Toshikazu Hirota, Yasuko Yoshida.
Application Number | 20080240946 12/149822 |
Document ID | / |
Family ID | 27750495 |
Filed Date | 2008-10-02 |
United States Patent
Application |
20080240946 |
Kind Code |
A1 |
Hirota; Toshikazu ; et
al. |
October 2, 2008 |
Microchemical chip
Abstract
A microchemical chip comprises a plate-shaped substrate, with a
channel formed on a surface of the substrate through which a fluid
flows. A fluid storage section for storing the fluid communicates
with the channel at a starting end of the channel. A fluid
discharge section communicates with the channel at a terminal end
of the channel. An extruding pump section is formed integrally on
the substrate, at a portion of the channel in the vicinity of the
fluid storage section.
Inventors: |
Hirota; Toshikazu;
(Nagoya-city, JP) ; Yoshida; Yasuko; (Nagoya-city,
JP) |
Correspondence
Address: |
OLIFF & BERRIDGE, PLC
P.O. BOX 320850
ALEXANDRIA
VA
22320-4850
US
|
Assignee: |
NGK INSULATORS, LTD.
Nagoya-city
JP
|
Family ID: |
27750495 |
Appl. No.: |
12/149822 |
Filed: |
May 8, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10504692 |
Aug 16, 2004 |
|
|
|
PCT/JP03/01692 |
Feb 18, 2003 |
|
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12149822 |
|
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Current U.S.
Class: |
417/413.3 |
Current CPC
Class: |
B01L 3/502746 20130101;
B01L 2400/0605 20130101; B01L 2400/0439 20130101; F04B 43/043
20130101; B01L 2400/0677 20130101; B01L 2300/0867 20130101; B01F
13/0059 20130101; B01L 3/502738 20130101; B01L 2300/0816 20130101;
B01L 3/50273 20130101; B01F 11/02 20130101; G01N 27/44704 20130101;
G01N 27/44791 20130101; F04B 53/1077 20130101; B01L 2400/082
20130101; B01L 2400/0421 20130101; B01L 2300/1827 20130101 |
Class at
Publication: |
417/413.3 |
International
Class: |
F04B 17/00 20060101
F04B017/00 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 19, 2002 |
JP |
2002-42391 |
Claims
1. A microchemical chip comprising one or more channels for
allowing a fluid to flow therethrough on a substrate, wherein: a
pump section is provided on an upstream side and/or a downstream
side of said channel; said pump section is formed integrally on
said substrate; a valve section is disposed on at least said
upstream side of said channel; said valve section is formed
integrally on said substrate; and said valve section has a
vibration-generating section for applying vibration to a part of
said channel.
2. The microchemical chip according to claim 1, further comprising
electrodes for performing electrophoresis on said fluid, disposed
on said upstream side and/or said downstream side of said
channel.
3. The microchemical chip according to claim 1, wherein said
channel includes one or more sample channels for allowing one or
more samples as inspection objectives to flow therethrough.
4. The microchemical chip according to claim 3, wherein said one or
more samples and a transport fluid, which correspond to said one or
more sample channels, flow through said one or more sample channels
respectively.
5. The microchemical chip according to claim 3, wherein a sample
supply section is provided for said one or more sample channels,
for supplying said one or more samples corresponding thereto
respectively.
6. The microchemical chip according to claim 5, wherein said
channel includes a merging channel, in which said one or more
samples are merged with each other from said one or more sample
channels.
7. The microchemical chip according to claim 6, further comprising
a vibration-generating section disposed at a portion at which
merging occurs.
8. The microchemical chip according to claim 6, wherein said valve
section has a heater for applying heat to a part of said
channel.
9. The microchemical chip according to claim 5, wherein said one or
more sample channels intersect with each other.
10. The microchemical chip according to claim 9, wherein a
vibration-generating section is provided at said location at which
intersecting occurs.
11. The microchemical chip according to claim 5, said sample supply
section comprises a nozzle having an outlet port that is arranged
to face one of said sample channels, and one of said samples is
supplied to the one of said sample channels through said outlet
port of said nozzle.
12. The microchemical chip according to claim 11, wherein said
sample supply section comprises: said nozzle; a supply cavity that
stores the one of said samples and makes communication with said
outlet port of said nozzle; and a supply actuator section that
varies a volume of said supply cavity and supplies the one of said
samples stored in said supply cavity to the one of said sample
channels through said outlet port of said nozzle.
13. The microchemical chip according to claim 1, wherein said
channel includes one or more sample channels for allowing one or
more samples as inspection objectives to flow therethrough
respectively, and one transport channel for allowing a transport
fluid for transporting said one or more samples to flow
therethrough.
14. The microchemical chip according to claim 13, wherein said
channel includes a merging channel in which said one or more
samples from said one or more sample channels are merged with said
transport fluid from said one transport channel, or a merging
channel in which a fluid obtained by mixing said one or more
samples from said one or more sample channels is merged with said
transport fluid from said one transport channel.
15. The microchemical chip according to claim 13, wherein said one
or more sample channels and said one transport channel intersect
with each other, or a merging channel of said one or more sample
channels and said one transport channel intersect with each
other.
16. The microchemical chip according to claim 1, wherein said valve
section has a heater for applying heat to a part of said
channel.
17. The microchemical chip according to claim 1, wherein said pump
section includes a pump cavity that makes communication with said
channel and allows the fluid flowing through said channel to flow
therethrough, and a pump actuator section that varies a volume of
said pump cavity.
18. The microchemical chip according to claim 17, wherein a valve
section is provided between said channel and said cavity, and said
valve section includes a valve plug arranged at a communicating
section between said channel and said cavity, and a valve actuator
section for operating said valve plug to selectively open and close
said communicating section.
19. A microchemical chip comprising one or more channels for
allowing a fluid to flow therethrough on a substrate, wherein: a
pump section is provided on an upstream side and/or a downstream
side of said channel; and said pump section is formed integrally on
said substrate, electrodes are disposed on said upstream side and
said downstream side of said channel, respectively, said electrodes
performing electrophoresis on said fluid in a direction opposite to
a transport direction by said pump.
20. The microchemical chip according to claim 19, wherein a valve
section is disposed on at least said upstream side of said channel,
said valve section includes a valve plug formed integrally on said
substance and arranged at said channel, a valve cavity formed on
said substrate, and a valve actuator section that varies a volume
of said valve cavity and displaces said valve plug in directions to
open and close said channel.
21. The microchemical chip according to claim 19, wherein a valve
section is disposed on at least said upstream side of said channel,
said valve section includes a valve cavity that is formed
integrally on said substrate, makes communication with said
channel, and allows the fluid flowing through said channel to flow
therethrough, and a valve actuator section that varies a volume of
said valve cavity.
22. The microchemical chip according to claim 19, wherein a valve
section is disposed on at least said upstream side of said channel,
said valve section has a vibration-generating section disposed
integrally on said substrate and applying vibration to a part of
said channel.
23. A microchemical chip comprising one or more channels for
allowing a fluid to flow therethrough on a substrate, wherein: a
supply section is provided for supplying the fluid to said channel;
a pump section is provided on an upstream side and/or a downstream
side of said channel; said pump section and said supply section are
formed integrally on said substrate; said supply section comprises
a nozzle having an outlet port that is arranged to face said
channel, and the fluid is supplied to said channel through said
outlet port of said nozzle.
24. The microchemical chip according to claim 23, wherein said
supply section comprises: said nozzle; a supply cavity that stores
the fluid and makes communication with said outlet port of said
nozzle; and a supply actuator section that varies a volume of said
supply cavity and supplies the fluid stored in said supply cavity
to the channel through said outlet port of said nozzle.
Description
[0001] This is a Continuation of application Ser. No. 10/504,692
filed Aug. 16, 2004, which in turn is a National Stage of
Application No. PCT/JP03/01692 filed Feb. 18, 2003. The disclosures
of the prior applications are hereby incorporated by reference
herein in their entirety.
TECHNICAL FIELD
[0002] The present invention relates to a microchemical chip, which
has one or more channels for allowing fluids to flow therethrough
on a substrate.
BACKGROUND ART
[0003] Recently, research and development are advancing with
respect to microchemical chips, on which chemical experiments are
performed using a palm-sized chip (square or rectangle of several
centimeters).
[0004] The microchemical chip includes a minute channel formed on a
surface of a substrate, which is composed of, for example, glass or
quartz. When a sample is supplied to the channel, so that the
sample is moved toward a downstream side, biochemical experiments
can be performed on the chip, including, for example, separation of
sample components, reaction, purification, and genetic
analysis.
[0005] Known measurement techniques that can be used on the
microchemical chip include several techniques, such as
electrophoresis and flow cytometry.
[0006] When the microchemical chip is used, an advantage is
obtained in that results can be obtained in a shorter period of
time with an extremely small amount of sample, as compared to other
conventional experimental equipment.
[0007] When the sample is moved through the channel formed on the
surface of the substrate of the conventional microchemical chip,
the following procedure is adopted. That is, a large-sized pump is
installed outside the substrate, and the sample is forcibly
injected, or the sample is forcibly sucked by using the large-sized
pump. Alternatively, the sample is moved, for example, in
accordance with an electroosmotic flow generated in a sample
solvent by applying a voltage between electrodes that are arranged
at an inlet and an outlet of the channel.
[0008] When a large-sized pump is used, an analytical device, which
includes the microchemical chip, also becomes large-sized, which
results in an increase in costs. Further, in the case of the
large-sized pump, the movement speed of the sample can be adjusted
inevitably roughly, which results in deterioration of analytical
accuracy, as well as deterioration in the efficiency of use of the
expensive sample.
[0009] When electroosmotic flow is used, it is usually necessary
that an extremely high electric field, of about several hundreds of
volt/cm, be applied as a voltage between electrodes, which also
results in large equipment size and high cost. Further, it is
necessary to pay attention to the handling of such equipment, in
view of safety. The entire sample solution flows toward a cathode
utilizing Coulomb's force. Therefore, for example, when
electrophoresis inspection is performed, this procedure is
adaptable when the sample (solute), which serves as the inspection
objective, is a negatively charged substance (DNA or protein).
However, in the case of a positively charged substance, or a
substance having no electric charge (for example, cells), it is
difficult to cause a difference in mobility of the inspection
objective. As a result, a problem arises in that resolution of the
inspection is deteriorated.
[0010] The movement speed of the sample solution is generally about
several hundreds to several thousands of picoliters per second, in
the case of a channel having a cross-sectional area of several
hundreds to several thousands square microns. In this situation,
high speed inspection cannot be satisfactorily achieved.
[0011] When the sample is supplied from the outside into the
channel using a conventional microchemical chip, the sample is
dispensed into an injection port, having an opening of several
millimeters to several centimeters .phi., by using a commercially
available micropipette. However, realizing a decrease in amount of
sample is limited to about several hundreds to several thousands of
nanoliters, for each time the amount of sample is dispensed. It has
also been expected to realize an injection method, in which the
amount of an injected sample could be even more minute.
[0012] The present invention has been made taking the foregoing
problems into consideration, an object of which is to provide a
microchemical chip which makes it possible to realize a small-sized
chip, improve analytical accuracy with respect to a sample and
highly accurately analyze the sample irrelevant to any electric
charge, which makes it possible to greatly shorten the inspection
time, and which makes it possible to realize multiple channels.
[0013] Another object of the present invention is to provide a
microchemical chip, which makes it possible to supply a more minute
amount of sample from the outside, further improve efficiency of
use of the sample and improve analytical accuracy, and to realize
high speed analysis, in addition to the objects described
above.
DISCLOSURE OF THE INVENTION
[0014] The present invention lies in providing a microchemical
chip, comprising one or more channels for allowing a fluid to flow
therethrough on a substrate, wherein a pump section is provided on
an upstream side and/or a downstream side of the channel, and
wherein the pump section is formed integrally on the substrate.
[0015] Because the pump section is formed integrally on the
substrate, the pump section can be used for providing charging or
injection of fluid into the channel, or to perform discharge or
suction of the fluid from the channel. It is unnecessary to install
a large-sized pump outside of the substrate. As a result, it is
possible to achieve a small size for the chip.
[0016] The amount of movement of the fluid can be adjusted
inevitably roughly when using a large-sized pump. However, in the
case of the pump section, which is integrally formed on the
substrate, it is possible to decrease the adjustable unit flow rate
(resolution) as compared with the amount of fluid flowing through
the channel. Therefore, it is possible to more accurately adjust
the amount of movement of the fluid. The movement speed of the
fluid can be freely varied using a driving signal supplied to the
pump. It is possible to realize a movement speed of from several
picoliters per second to several microliters per second. Further,
it is unnecessary to apply an extremely high electric field, of
several hundred volts/cm, in order to move the fluid. It is
possible to avoid a large size and high cost for the device.
Further, it is easy to handle the device in terms of safety.
[0017] Further, since the fluid can be moved using the pump
section, it is a matter of course that a fluid having no electric
charge can also be moved. Therefore, no inconvenience arises, which
would be otherwise caused if the inspection accuracy were affected
by the state of electric charge and the component of the sample
(solute) during electrophoresis inspection.
[0018] In the microchemical chip constructed as described above, it
is preferable that the microchemical chip further comprises a valve
section disposed on at least an upstream side of the channel,
wherein the valve section is formed integrally on the substrate.
Accordingly, when a valuable or expensive fluid is handled, the
amount of fluid supplied to the channel can be arbitrarily adjusted
using the valve section. Thus, it is possible to improve efficiency
of use of the sample and to reduce costs.
[0019] In the microchemical chip constructed as described above, it
is preferable that the microchemical chip further comprises
electrodes for performing electrophoresis on the fluid, at an
upstream side and/or a downstream side of the channel. This
arrangement is preferably adopted in order to perform
electrophoresis inspection, wherein inspection accuracy is not
affected by the state of electric charge and the component of the
sample (solute). For example, in the case of DNA or a protein in
which the sample (solute) serving as the inspection objective is
negatively charged, it is also possible to finely control the
amount of movement of the fluid with respect to the sample, by
reversing the direction of electrophoresis so as to be opposite to
the direction of movement effected by the pump section. Thus, it is
possible to improve inspection accuracy. That is, when an
electrode, which is disposed in the direction of movement of the
fluid controlled by the pump section, is made negative, the force
acts such that the sample itself is attracted in a direction
opposite to the flow (i.e., toward the positive electrode). Thus,
the ability of separation is improved.
[0020] When the fluid itself has a polarity, movement is caused by
electroosmotic flow, in addition to movement of the fluid effected
by the pump, by adjusting the intensity of the electric field
applied between the electrodes. It is possible to complete the
analysis, and movement of fluid, more effectively at high
speeds.
[0021] When the sample (solute) serving as the inspection objective
is positively charged, a force acts so that the sample itself is
attracted in a direction opposite to the flow (i.e., toward the
negative electrode) when an electrode, which is disposed in a
direction of movement of the fluid effected by the pump section, is
made positive. Thus, it is possible to ensure sufficient sample
separation.
[0022] In the microchemical chip constructed as described above, it
is also preferable that one or more sample channels are provided
for allowing one or more samples, serving as inspection objectives,
to flow therethrough. Accordingly, multiple channels can be easily
realized.
[0023] In the microchemical chip constructed as described above, it
is also preferable that samples and transport fluids, which
correspond to one or more sample channels, flow through one or more
sample channels respectively. Accordingly, valuable or expensive
samples can be conserved. Experiments can be efficiently performed,
and thus the arrangement is advantageous in view of cost. Further,
the sample supplied to a given channel can be mixed with a sample
supplied from another channel, by adjusting the supply timing of
the samples.
[0024] In the microchemical chip constructed as described above, it
is also preferable that a sample supply section be provided for one
or more sample channels, in order to supply the samples
corresponding thereto respectively. Accordingly, it is possible to
arbitrarily and accurately set the supply amount and supply timing
of minute sample amounts (i.e., at the picoliter level) to the
sample channels. This makes it possible to finely control, for
example, biochemical reactions in the channels. This further
results in an improvement in accuracy of the experiment,
inspection, and analysis, decrease in inspection time, and decrease
in cost.
[0025] In the microchemical chip constructed as described above, it
is also preferable that the channels include a merging channel, in
which one or more samples are merged with each other from one or
more sample channels. It is easy to perform, for example, reaction
and analysis as a result of merging a large number of samples.
[0026] In the microchemical chip constructed as described above, it
is also preferable that the channels include one or more sample
channels for allowing one or more samples, serving as inspection
objectives, to flow therethrough respectively, and a transport
channel for allowing a transport fluid for transporting the samples
to flow therethrough.
[0027] In this arrangement, it is also preferable that the channels
include a merging channel, in which one or more samples from one or
more sample channels are merged with the transport fluid from the
transport channel, or a merging channel in which a fluid obtained
by mixing one or more samples from one or more sample channels is
merged with the transport fluid from the transport channel. When
the sample channels and the transport channel are formed
separately, it is possible to select, for example, the material and
the shape, which are optimum for the physical properties of the
respective fluids. Such movement and merging can be performed while
saving valuable or expensive samples more effectively. It is
possible to perform experiments more efficiently. Further, the
arrangement is advantageous in view of cost.
[0028] In the microchemical chip constructed as described above, it
is also preferable that each of the one or more sample channels has
a valve section therein, disposed at an upstream stage of the
merging channel. Accordingly, it is possible to arbitrarily and
reliably adjust the movement of valuable or expensive fluids into
the merging portion by using the valve section. Alternatively, it
is also preferable that the microchemical chip further comprises a
vibration-generating section, disposed in an area at which merging
occurs. It is possible to enhance merging efficiency of one or more
samples within the merging area, and it is possible to improve, for
example, mixing speed, biochemical reaction speed, and inspection
speed, while more reliably performing mixing to thereby enhance the
biochemical reaction. The location where the vibration-generating
section is formed may be any one of an upper surface, a flat
surface, a side surface, or the entire circumferential surface,
provided that the location exists on at least a part of a wall
surface of the channel of the merging portion.
[0029] Further, one or more sample channels may intersect each
other. Alternatively, one or more sample channels and the transport
channel may intersect each other, or a merging channel of one or
more sample channels and the transport channel may intersect each
other. By doing so, a pump is provided for every channel. It is
possible to control drive timing of the pump, along with the
suction and discharge force of the pump, separately for each
channel, and/or it is possible to combine the above. It is possible
to mix the sample at the intersecting portion and/or it is possible
to effect movement from one channel to another channel. Further, in
this arrangement, it is preferable that each of the sample channels
has a valve section disposed upstream of the intersecting portion.
Accordingly, it is possible to arbitrarily and reliably adjust
movement of valuable or expensive fluids into the intersecting
portion using the valve section. It is possible to more reliably
move the sample from one channel to the other channel. Further, it
is also preferable that a vibration-generating section be provided
at the intersecting portion. With this arrangement, it is possible
to enhance mixing efficiency of one or more samples at the
intersecting portion. It is further possible to enhance the
biochemical reaction and improve inspection speed. The location
where the vibration-generating section is formed may be any one of
an upper surface, a flat surface, a side surface, or the entire
circumferential surface, provided that the location exists on at
least a part of a wall surface of the channel at the intersecting
portion.
[0030] In the microchemical chip constructed as described above, it
is also preferable that the valve section has a heater, which
applies heat to a part of the channel. As a result, a change in
flow passage resistance, caused by changing the viscosity of the
fluid, is effected by heat. When electric power is applied to the
heater, so that a portion of the channel in the vicinity of the
heater is heated, then the fluid viscosity is generally lowered,
and the fluid flows through the channel. On the other hand, when
application of electric power to the heater is stopped, so that the
valve section is cooled, the viscosity of the fluid is raised. As a
result, flow passage resistance is raised, and the flow of fluid is
stopped. In other words, fluid flow can be controlled by applying
or stopping the supply of electric power to the heater, thereby
functioning as a valve section.
[0031] It is also preferable that the valve section has a
vibration-generating section, which applies vibration to a part of
the channel. Thus, a change in flow passage resistance is effected
by such vibration. When vibration is applied to a part of the
channel, flow passage resistance is increased, and therefore, the
flow of fluid is stopped. The location where the
vibration-generating section is formed may be any one of an upper
surface, a flat surface, a side surface, or the entire
circumferential surface, provided that the location exists on at
least a part of a wall surface of the channel.
[0032] It is also preferable that the valve section includes a
cavity, which makes communication with the channel, and an actuator
section that varies the volume of the cavity. With such an
arrangement, as described above, operation timing may be
synchronized between the actuator of the valve section and the pump
section. That is, the actuator is operated at a predetermined
timing, so that a force is exerted to cause the fluid in the cavity
to flow in an opposite direction (i.e., a direction opposite to the
direction of flow of the fluid effected by the pump section),
whereby the volume of the cavity is decreased by operation of the
actuator section when the fluid in the channel is moved by the pump
section. As a result, it is possible to stop the flow of fluid by
the aid of the valve section.
[0033] When the valve section is constructed by a heater, a
vibration-generating section, or an actuator section, as described
above, reliable operation can be realized with a more simple and
inexpensive structure, as compared with the conventional mechanical
valve. On the other hand, such a construction is also excellent in
durability.
[0034] Further, it is preferable that each of the pump section and
the sample supply section comprises a nozzle, a cavity that makes
communication with a channel, and a pump actuator section that
varies the volume of the cavity. With this arrangement, when the
volume of the cavity is decreased by operation of the actuator
section, fluid in the cavity is forced to flow toward a downstream
side. In addition, when the volume of the cavity is expanded or
returned to its original volume, fluid on an upstream side is
attracted into the cavity. By successively repeating the above
operations, fluid on an upstream side of the cavity is caused to
flow successively toward a downstream side thereof.
[0035] It is also preferable that a valve section be provided
between the channel and the cavity. With such an arrangement, the
valve section also includes a valve plug, which is arranged at a
communicating section where the channel and the cavity communicate
with each other, and a valve actuator section that operates the
valve plug to selectively open and close the communicating section.
Accordingly, the pump can move the fluid more conveniently and
efficiently. In particular, using this arrangement, it is easy to
fill an empty channel with fluid.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] FIG. 1 shows a perspective view illustrating a microchemical
chip according to a first embodiment;
[0037] FIG. 2 shows a sectional view illustrating a first pump
section;
[0038] FIG. 3 shows a sectional view illustrating a second pump
section;
[0039] FIG. 4 shows a perspective view illustrating a microchemical
chip according to a second embodiment;
[0040] FIG. 5 shows a sectional view illustrating a third pump
section;
[0041] FIG. 6 shows a sectional view illustrating a fourth pump
section;
[0042] FIG. 7 shows a perspective view illustrating a microchemical
chip according to a third embodiment;
[0043] FIG. 8 shows a sectional view illustrating a structure of a
main supply section of a sample supply section;
[0044] FIG. 9 shows a perspective view illustrating a microchemical
chip according to a fourth embodiment;
[0045] FIG. 10 shows a perspective view illustrating a modified
embodiment of the microchemical chip according to the fourth
embodiment;
[0046] FIG. 11 shows a perspective view illustrating a
microchemical chip according to a fifth embodiment;
[0047] FIG. 12 shows a sectional view illustrating a structure of a
vibration-generating section;
[0048] FIG. 13 shows a perspective view illustrating a
microchemical chip according to a sixth embodiment;
[0049] FIG. 14 shows a sectional view illustrating a first check
valve;
[0050] FIG. 15 shows a sectional view illustrating a second check
valve;
[0051] FIG. 16 shows a perspective view illustrating a
microchemical chip according to a seventh embodiment;
[0052] FIG. 17 shows a perspective view illustrating a
microchemical chip according to an eighth embodiment;
[0053] FIG. 18 shows a perspective view illustrating a
microchemical chip according to a ninth embodiment;
[0054] FIG. 19 shows a sectional view illustrating a first valve
section;
[0055] FIG. 20 shows a sectional view illustrating a second valve
section; and
[0056] FIG. 21 shows a sectional view illustrating a third valve
section.
BEST MODE FOR CARRYING OUT THE INVENTION
[0057] An explanation will be made below with reference to FIGS. 1
to 21, which illustrate various embodiments of a microchemical chip
according to the present invention.
[0058] As shown in FIG. 1, a microchemical chip 10A according to a
first embodiment comprises a plate-shaped substrate 12, including
one channel 14 which is formed on a surface of the substrate 12,
wherein an upper surface thereof is closed with a transparent glass
plate, and wherein a fluid is allowed to flow through the channel
14. A fluid storage section 16, in which fluid is stored, is formed
at a starting end of the channel 14 and communicates with the
channel 14. A fluid discharge section 18, which also communicates
with the channel 14, is formed at the terminal end of the channel
14.
[0059] The fluid may include, for example, a single solution in
which a sample (solute), serving as an inspection objective, is
dissolved or dispersed, or a combination made up of the sample
solution as the inspection objective and a transport fluid. When a
transport fluid is used in addition to the sample, it is possible
to conserve expensive samples.
[0060] Materials usable as the sample may include, for example,
nucleic acids, proteins, saccharides, cells, and conjugated
thereof. The nucleic acids may include, for example, DNA and/or
fragments thereof as well as amplified products thereof, cDNA
and/or fragments thereof as well as amplified products thereof, RNA
or antisense RNA and/or fragments thereof as well as amplified
products thereof, synthetic DNA as well as amplified products
thereof, and synthetic RNA as well as amplified products thereof.
The proteins may include, for example, antigens, antibodies,
lectin, adhesin, receptors for bioactive substance substances, and
peptides.
[0061] Devices installed in the channel 14, which are usable for
performing chemical analysis such as chromatography, include, for
example, heat-generating sections, heating sections, cooling
sections, pH-adjusting sections, laser-irradiating sections,
radiation-emitting sections, and inspecting sections. FIG. 1 is
illustrative of a case in which three types of heat-generating
sections 20a to 20c are installed by way of example.
[0062] Materials for constructing the substrate 12 may include, for
example, glass, plastic, silicon (quartz), ceramics, and glass
ceramics. Among the materials described above, it is preferable to
use a glass material considering, for example, chemical durability
and transparency, as well as providing electric insulation in the
case that electrophoresis is used. For forming the channel 14 on
the surface of the substrate 12, it is possible to use an etching
method such as, for example, photolithography.
[0063] The glass material is selected taking into account its,
material properties which facilitate the formation of the channel
14 therein, and while also considering factors which affect the
fluid, including, for example, durability against weak acids and
weak alkalis, wettability, water repellence, surface tension,
elution of glass components, polarity of the glass surface, and the
surface group.
[0064] Various glasses are usable as the glass material, including,
for example, borosilicate glasses such as white board or white
sheet (BK 7), as well as glasses based on La, Zr, and Ti.
[0065] As shown in FIG. 1, in the first embodiment, an extruding
pump section 22 is formed integrally on the substrate 12, at a
portion of the channel 14 on an upstream side thereof, in the
vicinity of a fluid storage section 16.
[0066] Features of the extruding pump section 22 shall now be
explained. For example, first and second pump sections 22A, 22B can
be used as the pump section 22. An explanation will be made below
concerning the first and second pump sections 22A, 22B.
[0067] Details of the first pump section 22A are described in
Japanese Laid-Open Patent Publication No. 2000-314381, the content
of which is incorporated herein by reference. However, a brief
explanation will now be made. As shown in FIG. 2, the first pump
section 22A comprises a casing 30 made of, for example, a ceramic
and to which the fluid is supplied, an input valve 32, a pump 34,
and an output valve 36, which confront one surface of the casing
30. Each of the input valve 32, the pump 34, and the output valve
36 comprises an actuator section 38.
[0068] The casing 30 is constructed by stacking a plurality of
zirconia ceramic green sheets, and sintering them in an integrated
manner. The casing 30 includes a partition plate 40, which is
provided in contact with a surface of the substrate 12, a second
substrate 42, which opposes the partition plate 40, and a support
member 44, which is provided between the partition plate 40 and the
second substrate 42.
[0069] The first pump section 22A controls fluid flow by
selectively forming a flow passage on a back surface of the casing
30 by selectively displacing each of the input valve 32, the pump
34, and the output valve 36 in directions to approach and separate
from each other.
[0070] An inlet hole 46 for supplying fluid and a discharge hole 48
for discharging fluid are formed through the partition plate 40.
The input valve 32, the pump 34, and the output valve 36 are
arranged laterally between the inlet hole 46 and the discharge hole
48.
[0071] Hollow spaces 50, forming vibrating sections, are provided
respectively in the second substrate 42, at positions corresponding
to the input valve 32, the pump 34, and the output valve 36. Each
of the hollow spaces 50 communicates to the exterior via a small
diameter through-hole 52, which is provided at an end surface of
the second substrate 42.
[0072] Portions of the second substrate 42 where the hollow spaces
50 are formed are thin-walled, and the remaining portion of the
second substrate 42 is thick-walled. The thin-walled portions are
constructed so that vibration is easily received when an external
stress is applied, for functioning as a vibrating section 54. The
remaining portion, other than the hollow spaces 50, functions as a
fixed section 56 for supporting the vibrating section 54.
[0073] A plurality of unillustrated support pillars intervene
between the partition plate 40 and the second substrate 42 in the
vicinity of the actuator section 38, and thus rigidity is
maintained. In this embodiment, rigidity is further maintained by
the support member 44 of the casing 30.
[0074] Each of the actuator sections 38 comprises a vibrating
section 54 and a fixed section 56, as well as an operating section
66. The operating section 66 includes a shape-retaining layer 60,
such as a piezoelectric/electrostrictive layer or an
anti-ferroelectric layer formed on the vibrating section 54, and an
upper electrode 62 and a lower electrode 64, which are formed
respectively on upper and lower surfaces of the shape-retaining
layer 60.
[0075] The first pump section 22A includes a
displacement-transmitting section 68. The displacement-transmitting
section 68 is formed over each of the actuator sections 38, and
transmits displacement from each of the actuator sections 38 in a
direction toward a back surface of the casing 30.
[0076] For feeding fluid from an upstream side of the first pump
section 22A to a downstream side of the first pump section 22A, the
actuator section 38 of the input valve 32 is driven so that an end
surface portion of the displacement-transmitting section 68,
corresponding to the input valve 32, separates from the partition
plate 40. Subsequently, the actuator section 38 of the pump 34 is
driven so that an end surface portion of the
displacement-transmitting section 68, corresponding to the pump 34,
separates from the partition plate 40. Accordingly, fluid on the
upstream side flows toward the pump 34 by the aid of the input
valve 32.
[0077] Next, the actuator section 38 of the input valve 32 is
driven so that an end surface portion of the
displacement-transmitting section 68, corresponding to the input
valve 32, makes contact with the partition plate 40. Subsequently,
the actuator section 38 of the output valve 36 is driven so that an
end surface portion of the displacement-transmitting section 68,
corresponding to the output valve 36, separates from the partition
plate 40. Further, the actuator section 38 of the pump 34 is driven
so that an end surface portion of the displacement-transmitting
section 68, corresponding to the pump 34, makes contact with the
partition plate 40. Accordingly, fluid flows toward the output
valve 36.
[0078] Thereafter, the actuator section 38 of the output valve 36
is driven so that an end surface portion of the
displacement-transmitting section 68, corresponding to the output
valve 36, makes contact with the partition plate 40. Accordingly,
fluid flows inwardly, into a downstream side of the channel 14, via
the discharge hole 48.
[0079] The operations described above are successively repeated,
and thus fluid, which exists on an upstream side of the first pump
section 22A (in this case, in the fluid storage section 16),
successively flows toward a downstream side of the first pump
section 22A, i.e., toward a downstream side of the channel 14.
[0080] As shown in FIG. 3, the second pump section 22B comprises a
partition plate 70 in contact with a surface of the substrate 12, a
vibration plate 72 opposing the partition plate 70, and a support
member 74 disposed between the partition plate 70 and the vibration
plate 72. The partition plate 70, the vibration plate 72 and the
support member 74 are constructed by stacking a plurality of
zirconia ceramic green sheets, and sintering the sheets in an
integrated manner.
[0081] An operating section 76 is formed on an upper surface of the
vibration plate 72. The operating section 76 comprises a
shape-retaining layer 78, such as a piezoelectric/electrostrictive
layer or an anti-ferroelectric layer, and an upper electrode 80 and
a lower electrode 82 formed respectively on upper and lower
surfaces of the shape-retaining layer 78, in the same manner as in
the first pump section 22A described above. The vibration plate 72
and the operating section 76 together make up an actuator section
84.
[0082] A cavity 86, into which fluid is introduced, is formed under
the vibration plate, at a location corresponding to the operating
section 76. In other words, the cavity 86 is defined by the
partition plate 70, the vibration plate 72, and the support member
74, and the cavity 86 communicates with an inlet hole 88 and a
discharge hole 90, which are formed through the partition plate
70.
[0083] On the other hand, an input valve 92 and an output valve 94
are provided in the channel 14 of the substrate 12, at portions
corresponding to the inlet hole 88 and the discharge hole 90.
[0084] The input valve 92 comprises an actuator section 96 and a
conical displacement-transmitting section 98 provided on the
actuator section 96. The actuator section 96 further comprises a
hollow space 100 formed in the substrate 12, wherein the hollow
space 100 makes up a vibrating section 102 and a fixed section 104,
and wherein an operating section 106 is formed on the vibrating
section 102. Similarly, the output valve 94 also comprises an
actuator section 108 and a conical displacement-transmitting
section 110 provided on the actuator section 108.
[0085] The displacement-transmitting section 98 of the input valve
92 opens and closes the inlet hole 88 by displacing the actuator
section 96 of the input valve 92 in a vertical direction.
Similarly, the displacement-transmitting section 110 of the output
valve 94 opens and closes the discharge hole 90 by displacing the
actuator section 108 of the output valve 94 in a vertical
direction.
[0086] Therefore, fluid disposed on an upstream side of the second
pump section 22B is introduced into the cavity 86 by the aid of the
input valve 92 and the inlet hole 88. Further, fluid contained in
the cavity 86 flows downstream by the aid of the discharge hole 90
and the output valve 94, as a result of changing the volume of the
cavity 86 by driving of the actuator section 84.
[0087] In the microchemical chip 10A, the pump section 22 is formed
integrally on the substrate 12 on an upstream side of the channel
14. Therefore, it is possible to cause movement and charging of
fluid into the channel 14, while the microchemical chip 10A has the
same size as that of a conventional microchemical chip. Considering
fluid viscosity, movement can be performed with fluids having a
high viscosity of up to about one hundred thousand centipoises. It
is also possible to realize movement speeds ranging from 10
picoliters per second to a maximum of 10 microliters per
second.
[0088] Next, as shown in FIG. 4, a microchemical chip 10B according
to a second embodiment is constructed in approximately the same
manner as the microchemical chip 10A described above. However, the
microchemical chip 10B differs in that a suction pump section 22 is
formed integrally on the substrate 12 on a downstream side of the
channel 14, i.e., in the vicinity of the fluid discharge section 18
of the channel 14.
[0089] As shall be described below, the pump section 22 may also
include third and fourth pump sections 22C, 22D in addition to the
aforementioned first and second pump sections 22A, 22B.
[0090] Details of the third pump section 22C are described, for
example, in Japanese Laid-Open Patent Publication No. 2001-124789,
the content of which is incorporated herein by reference. However,
a brief description will now be made below. As shown in FIG. 5, the
third pump section 22C comprises a partition plate 120 provided in
contact with a surface of the substrate 12, a vibration plate 122
opposed to the partition plate 120, and a support member 124
disposed between the partition plate 120 and the vibration plate
122. The partition plate 120, the vibration plate 122 and the
support member 124 may be constructed by stacking a plurality of
zirconia ceramic green sheets, and sintering the sheets in an
integrated manner.
[0091] An operating section 126 is formed on an upper surface of
the vibration plate 122. The operating section 126 comprises a
shape-retaining layer 128, such as a piezoelectric/electrostrictive
layer or an anti-ferroelectric layer, and an upper electrode 130
and a lower electrode 132 formed on upper and lower surfaces of the
shape-retaining layer 128, in the same manner as the first pump
section 22A described above. The vibration plate 122 and the
operating section 126 together make up an actuator section 134.
[0092] A cavity 136, into which a fluid is introduced, is formed
under the vibration plate 122 at a location corresponding to the
operating section 126. In other words, the cavity 136 is defined by
the partition plate 120, the vibration plate 122 and the support
member 124, and the cavity 136 communicates with an inlet hole 138
and a discharge hole 139 that are formed through the partition
plate 120.
[0093] For feeding fluid introduced on an upstream side of the
third pump section 22C to a downstream side of the third pump
section 22C, the actuator section 134 is driven to decrease the
volume of the cavity 136. Accordingly, fluid contained in the
cavity 136 is forced to flow downstream. When the actuator section
134 is driven to expand the volume of the cavity 136, or to return
the cavity 136 to its original volume, fluid on the upstream side
is introduced into the cavity 136. The operations described above
are successively repeated, and thus fluid on the upstream side
successively flows downstream.
[0094] On the other hand, as shown in FIG. 6, the fourth pump
section 22D comprises a partition plate 140 provided in contact
with a surface of the substrate 12, an upper plate 142 opposing the
partition plate 140, and side walls 144 disposed between the
partition plate 140 and the upper plate 142.
[0095] Side walls 144 are composed of a
piezoelectric/electrostrictive material or an anti-ferroelectric
material. Although not shown, electrode films are formed on the
side walls 144. When voltage is supplied to the electrode films and
an electric field is applied to the side walls 144, the side walls
144 are expanded/contracted in a vertical direction, depending on
the intensity of the electric field.
[0096] A volume surrounded by the partition plate 140, the side
wall 144 and the upper plate 142 forms a cavity 146 for introducing
a fluid thereinto. The cavity 146 communicates with an inlet hole
148 and a discharge hole 150 provided in the partition plate
140.
[0097] The inlet hole 148 has a diameter that is progressively
smaller toward the cavity 146, wherein the opening diameter facing
the channel 14 is larger than the opening diameter facing the
cavity 146. Similarly, the discharge hole 150 has a diameter that
is progressively larger toward the cavity 146, wherein the opening
diameter facing the channel 14 is smaller than the opening diameter
facing the cavity 146. In other words, the inlet hole 148 is
structured such that fluid disposed on an upstream side enters
easily into the cavity 146 via the inlet hole 148, whereas fluid
contained in the cavity 146 is not easily discharged via the inlet
hole 148. The discharge hole 150 is structured such that fluid
contained in the cavity 146 is easily discharged downstream via the
discharge hole 150, whereas fluid on the downstream side is
prevented from entering the cavity 146 via the discharge hole
150.
[0098] For feeding fluid on an upstream side of the fourth pump
section 22D downstream of the fourth pump section 22D, a positive
electric field is applied to the side walls 144 in order to shrink
the side walls 144, whereby the volume of the cavity 146 decreases.
Accordingly, fluid contained in the cavity 146 is forced to flow
downstream. When a negative electric field is applied to the side
walls 144 in order to elongate the side walls 144, the volume of
the cavity 146 expands or is returned to its original volume.
Accordingly, fluid on the upstream side is attracted into the
cavity 146. By successively repeating the above operations, fluid
on the upstream side flows successively downstream.
[0099] The microchemical chip 10B is small in size, in the same
manner as the microchemical chip 10A described above. Further, the
microchemical chip 10B can be constructed conveniently and
inexpensively, because the pump section 22 does not require a valve
structure. Durability of the microchemical chip 10B is also
improved. As has been noted, the pump section 22 of the
microchemical chip 10B has no valve structure, and therefore, fluid
cannot be extruded. The microchemical chip 10B operates as a
suction pump, wherein the downstream side thereof resides at
atmosphere and the upstream side is filled with fluid, as
illustrated in the above embodiment. Fluid can be moved having a
viscosity up to about 1,000 centipoises. Movement speeds, ranging
from 1 picoliter per second to a maximum of 10 microliters per
second, have been successfully realized. When experiments and
analyses were performed using microchemical chips 10A and 10B,
improvements in analytical accuracy and biochemical analysis were
achieved using fluids having no electric charge.
[0100] Next, a microchemical chip 10C according to a third
embodiment will be explained with reference to FIG. 7.
[0101] The microchemical chip 10C is constructed in approximately
the same manner as the microchemical chip 10B described above.
However, the microchemical chip 10C differs in that a sample supply
section 160 is provided in order to supply the sample to the
channel 14.
[0102] The sample supply section 160 comprises a main supply
section 162 formed within an opening making up a part of the
channel 14 and disposed on an upper surface thereof, a sample
storage section 164 formed on the surface of the substrate 12, and
a sample channel 166 for introducing a sample from the sample
storage section 164 to the main supply section 162.
[0103] As shown in FIG. 8, the main supply section 162 further
comprises a ceramic casing 170 formed on the surface of the
substrate 12. The casing 170 is constructed by stacking a plurality
of ceramic green sheets, and sintering the sheets in an integrated
manner. Inside the casing 170 are first and second cavities 172,
174, which temporarily store the sample supplied from the sample
channel 166, a communication hole 176 communicating between the
first and second cavities 172, 174, and a sample discharge hole 178
which is directed toward an opening of the channel 14.
[0104] The main supply section 162 further includes an actuator
section 177, which vibrates the casing 170 and/or which changes the
volume of the second cavity 174. The second cavity 174 is defined
by a lower plate 180 in which the sample discharge hole 178 and the
communication hole 176 are formed, an upper plate 184 (vibration
plate) positioned over the second cavity 174, and a side plate 182
arranged between the lower plate 180 and the upper plate 184. The
actuator section 177 is formed on a surface of the upper plate
184.
[0105] In the main supply section 162 constructed as described
above, when the volume of the second cavity 174 decreases by
driving the actuator section 177, the sample contained in the
second cavity 174 is discharged at a predetermined speed from the
sample discharge hole 178, and the sample is supplied to the
channel 14. When the actuator section 177 is driven to expand the
volume of the second cavity 174 or to return the second cavity 174
to its original volume, the sample contained in the first cavity
172 is introduced into the second cavity 174 via the communication
hole 176, and further, the sample contained in the sample storage
section 164 is introduced into the first cavity 172 via the sample
channel 166. When the operations described above are successively
repeated, the sample contained in the sample supply section 160 is
successively supplied to the channel 14.
[0106] In this arrangement, the size of the main supply section 162
is selected depending on, for example, the overall size of the
microchemical chip and the type of the sample to be handled.
However, when the size of the cavity 174 is such that its width is
3 mm, its length is 0.3 mm, and its thickness is 0.3 mm, and
wherein the sample discharge hole 178 and the communication hole
176 have diameters of 0.07 mm, then the sample may be supplied in
an amount of 100 picoliters per each driving of the actuator
section 177, provided the viscosity of the sample is 2
centipoises.
[0107] In the microchemical chip 10C, the sample supply section 160
may be used to arbitrarily set the supply timing of the sample to
the channel 14, and the supplied amount of sample may be in units
of picoliters. The microchemical chip 10C has been successfully
provided while reducing costs, and also enabling a more minute
amount of sample to be supplied from the outside. Further, high
speed analysis, improvement in analytical accuracy, and efficiency
of use of the sample can be realized.
[0108] Further, in the microchemical chip 10C, the pump section 22
is not always essential. Electroosmotic flow may also be utilized,
or a conventional external pump may be used for moving the fluid in
the channel 14.
[0109] Next, a microchemical chip 10D according to a fourth
embodiment will be explained with reference to FIG. 9.
[0110] As shown in FIG. 9, the microchemical chip 10D is
constructed in approximately the same manner as the microchemical
chip 10A described above. However, the microchemical chip 10D
differs in that two fluid storage sections (first and second fluid
storage sections 16A, 16B) are provided, and respective pump
sections 22 are formed in the vicinity of the fluid storage
sections 16A, 16B. The first and second pump sections 22A, 22B
shown in FIGS. 2 and 3 can be used as the pump sections 22.
[0111] That is, as shown in FIG. 9, the microchemical chip 10D
comprises a first channel 14a for feeding fluid contained in the
first fluid storage section 16A downstream, a second channel 14b
for feeding fluid contained in the second fluid storage section 16B
downstream, and a merging channel 14 at which two types of fluids,
fed through the first and second channels 14a, 14b, are merged
together.
[0112] For example, when a sample, serving as an inspection
objective, is supplied to the first fluid storage section 16A,
another sample, also serving as an inspection objective, may be
supplied to the second fluid storage section 16B. With this
arrangement, it is possible to easily perform, for example,
biochemical analysis, as a result of merging (and, for example,
causing reaction between) the two types of samples. Of course, a
transport fluid may also be supplied to the second fluid storage
section 16B. In this case, a sample is moved to the merging point
using the pump section 22 installed in the first channel 14a,
whereas the transport fluid is continuously supplied using the pump
section 22 installed in the second channel 14b. Accordingly, the
sample per se, which has been moved to the merging point, can be
more efficiently utilized when performing, for example, separation,
reaction and analysis.
[0113] As shown in FIG. 10, a microchemical chip 10Da according to
a modified embodiment comprises, for example, three fluid storage
sections 16A to 16C provided on the surface of the substrate 12,
together with first to third channels 14a to 14c and a merging
channel 14. Accordingly, mutually different samples may be supplied
to the first and second channels 14a, 14b respectively, and a
transport fluid may be supplied to the third channel 14c.
Therefore, it is easy to inspect the result after merging of
different samples, while conserving valuable or expensive samples.
Of course, four or more channels, and one or more merging channels,
may also be provided.
[0114] Next, as shown in FIG. 11, a microchemical chip 10E
according to a fifth embodiment shall be described. The
microchemical chip 10E is constructed in approximately the same
manner as the microchemical chip 10D described above. However, the
microchemical chip 10E differs in that a vibration-generating
section 190 is provided at the merging portion. As shown in FIG.
12, for example, the vibration-generating section 190 comprises a
vibration plate 192 provided at a merging portion of the channel
14, and an operating section 194 (made up of a shape-retaining
layer 196, an upper electrode 198, and a lower electrode 200)
formed on the vibration plate 192. When alternating voltage is
applied to the upper electrode 198 and the lower electrode 200,
vibration is easily generated at the merging portion. The vibration
plate 192 is essential if the operating section 194 is formed by
means of integrated sintering. However, the vibration plate 192 is
not essential when, for example, the operating section 194 is
manufactured using electrodes that are formed on a bulk
piezoelectric material. The operating section 194 may also be
directly adhered to the channel 14. The vibration-generating
section 190 may be installed, for example, on a side surface or a
bottom surface, rather than being installed at an upper portion of
the channel 14. In particular, when the substrate 12 is composed of
zirconia ceramics, the vibration-generating section 190 may also be
formed integrally with the pump section 22.
[0115] Further, in the microchemical chip 10E, it is possible to
enhance mixing and merging efficiency of two different types of
samples at the merging portion, by applying vibration to the
merging portion, wherein reaction and inspection speed have been
successfully improved.
[0116] Next, a microchemical chip 10F according to a sixth
embodiment will be explained with reference to FIG. 13.
[0117] As shown in FIG. 13, the microchemical chip 10F is
constructed in approximately the same manner as the microchemical
chip 10B described above. However, the microchemical chip 10F
differs in that two fluid storage sections (first and second fluid
storage sections 16A, 16B) are provided, wherein check valves 210
are formed in the vicinity of the respective fluid storage sections
16A and 16B. Any one of the first to fourth pump sections 22A to
22D, shown in FIGS. 2 and 3 or FIGS. 5 and 6, can be used as the
pump section 22.
[0118] The microchemical chip 10F also includes a first channel 14a
feeding fluid contained in the first fluid storage section 16A
downstream, a second channel 14b feeding fluid contained in the
second fluid storage section 16B downstream, and a merging channel
14 where two fluids fed through the first and second channels 14a,
14b are merged.
[0119] A first check valve 210A shown in FIG. 14 and/or a second
check valve 210B shown in FIG. 15 can be used as the check valve
210. Features of the check valve 210 shall now be explained,
assuming that the substrate 12 is covered with a lid plate 212, for
closing at least channels 14a and 14b.
[0120] As shown in FIG. 14, the first check valve 210A comprises a
main valve body 214 provided in channels 14a, 14b of the substrate
12.
[0121] The main valve body 214 comprises an upper plate 216, side
walls 218 provided between the substrate 12 and the upper plate
216, and a conical displacement-transmitting section 220 disposed
on the upper plate 216. A conical recess 222 is formed in a portion
of the lid plate 212, corresponding in location to the
displacement-transmitting section 220.
[0122] Side walls 218 are composed of a
piezoelectric/electrostrictive material or an anti-ferroelectric
material. Although not shown, electrode films are formed on the
side walls 218. When a voltage is supplied to the electrode films
to apply an electric field to the side walls 218, the side walls
218 are expanded/contracted vertically depending on the intensity
of the electric field.
[0123] When the displacement-transmitting section 220 contacts the
inner surface of the recess 222 by applying a negative electric
field to elongate the side walls 218, the flow of fluid is stopped.
By contrast, when the displacement-transmitting section 220
separates from the recess 222 by applying a positive electric field
to contract the side walls 218, flow of fluid through the channel
14a (14b) resumes.
[0124] On the other hand, as shown in FIG. 15, the second check
valve 210B comprises a main valve body 230 provided in channels
14a, 14b of the substrate 12.
[0125] The main valve body 230 comprises an actuator section 232,
and a conical displacement-transmitting section 234 disposed on the
actuator section 232. The actuator section 232 includes a hollow
space 236 formed in the substrate 12, wherein a vibrating section
238 and a fixed section 240 are formed as a result of the hollow
space 236. An operating section 242 is formed on the vibrating
section 238.
[0126] The displacement-transmitting section 234 contacts with or
separates from the recess 222 by vertically displacing the actuator
section 232 of the main valve body 230. Thus, flow of fluid may be
stopped or advanced.
[0127] As shown in FIG. 13, a sample, serving as an inspection
objective, and a transport fluid may be supplied to the first fluid
storage section 16A. Another sample, serving as a different
inspection objective, and another transport fluid may be supplied
to the second fluid storage section 16B. Using this procedure, for
example, biochemical analysis can be easily performed as a result
of merging (e.g., causing reaction between) two types of samples.
The respective check valves 210 can be used to arbitrarily adjust
the amounts at which the samples are supplied to the respective
channels 14a, 14b. Accordingly, analytical accuracy can be improved
while reducing cost.
[0128] Alternatively, for example, a sample serving as an
inspection objective may be supplied to the first fluid storage
section 16A, and a transport fluid may be supplied to the second
fluid storage section 16B. Also in this case, the check valves 210
can be used to arbitrarily adjust the amounts of the sample and the
transport fluid that are supplied to the respective channels 14a,
14b.
[0129] Next, a microchemical chip 10G according to a seventh
embodiment will be explained with reference to FIG. 16.
[0130] As shown in FIG. 16, the microchemical chip 10G is
constructed in approximately the same manner as the microchemical
chip 10B described above. However, the microchemical chip 10G
differs in that electrodes 250, 252 are formed on upstream and
downstream sides of the channel 14.
[0131] Specifically, one electrode 250 is formed in the vicinity of
the fluid storage section 16, and the other electrode 252 is formed
upstream of the pump section 22 of the channel 14. When a sample,
serving as the inspection objective, comprises a solute having an
electric charge, wherein the sample has a negative charge, for
example, then one electrode 250 operates as an anode (i.e., an
electrode having a higher electric potential) and the other
electrode 252 operates as the cathode. Accordingly, the sample is
moved by electrophoresis in a direction opposite to the direction
of movement caused by the pump section 22.
[0132] As described above, in the microchemical chip 10G, when the
direction of electrophoresis is opposite to the direction of
movement caused by the pump section 22, a force acts to attract the
sample per se in a direction opposite to the direction of flow
(i.e., toward the positive electrode). Thus, the separation ability
during electrophoresis analysis can be improved.
[0133] When the fluid itself has a given polarity, movement is
caused by electroosmotic flow, in addition to movement of the fluid
caused by the pump, by adjusting the intensity of the electric
field applied between the electrodes. Thus, high speed movement of
fluid and rapid completion of analysis can be realized more
effectively.
[0134] When a sample (solute) serving as the inspection objective
is positively charged, a force acts to attract the sample per se in
a direction opposite to the direction of flow (i.e., toward the
negative electrode), by making the electrode that influences the
movement direction of the pump section 22 to be positive. Thus,
sufficient ability of separation can be secured.
[0135] Next, a microchemical chip 10H according to an eighth
embodiment will be explained with reference to FIG. 17.
[0136] As shown in FIG. 17, the microchemical chip 10H is
constructed in approximately the same manner the microchemical chip
10B described above. However, the microchemical chip 10H differs in
that another channel 260 is formed, which intersects with the
channel 14, and electrodes 250, 252 are provided on upstream and
downstream sides of the additional channel 260.
[0137] Specifically, one electrode 250 is formed in the vicinity of
a fluid storage section 262, and the other electrode 252 is formed
in the vicinity of a fluid discharge section 264 disposed in the
other channel 260. When a sample serving as the inspection
objective comprises a fluid having a given electric charge, for
example, when the sample has a negative charge, then one electrode
250 is used as a cathode (i.e., an electrode having a lower
electric potential), and the other electrode 252 is used as an
anode. Accordingly, electroosmotic flow is generated in a direction
toward the fluid discharge section 264.
[0138] When a sample irrespective its of electric charge is
supplied to one channel 14, and a sample having an electric charge
is supplied to the other channel 260, then the samples are mixed
with each other at the intersecting portion. Further, the mixed
fluid flows toward a downstream side of the channel 14, while using
one channel 14. Accordingly, biochemical analysis can be performed
on the mixed fluid.
[0139] Of course, when a vibration-generating section 190 (see FIG.
11) is formed at the intersecting portion, efficiency of the
reaction and mixing of the two types of samples at the intersecting
portion can be enhanced. Thus, it is possible to improve inspection
speed and enhance the experiment.
[0140] In the microchemical chip 10H, when the sample is separated
and moved by the pump section 22, using the transport fluid
supplied to the intersecting portion from the fluid storage section
16 via the channel 14, and after the sample is supplied to the
intersecting portion from the fluid storage section 262 using
electroosmotic flow as described above, sample fluid, apart from
the sample actually supplied to the crossing portion, can be
prevented from flowing out of the channel 14 by reversing the
voltage applied to the electrodes during a period in which the pump
section 22 is operated.
[0141] Next, a microchemical chip 10I according to a ninth
embodiment will be explained with reference to FIG. 18.
[0142] As shown in FIG. 18, the microchemical chip 10I is
constructed in approximately the same manner as the microchemical
chip 10F described above. However, the microchemical chip 10I
differs in that a valve section 300 is formed in a first channel
14a through which a sample serving as the inspection objective
flows. In other words, the valve section 300 is not formed in the
second channel 14b, through which the transport fluid flows.
Rather, the valve section 300 is formed only in the first channel
14a to which a valuable or expensive sample is supplied.
[0143] The valve section 300 may comprise, for example, the first
valve section 300A shown in FIG. 19, the second valve section 300B
shown in FIG. 20, or the third valve section 300C shown in FIG.
21.
[0144] As shown in FIG. 19, the first valve section 300A comprises
a flow passage resistor 302 made of, for example, ceramic, and a
heater 304 embedded in the flow passage resistor 302.
[0145] The first valve section 300A utilizes change in flow passage
resistance resulting from a viscosity change of the fluid caused by
heat. When electric power is applied to the heater 304 to heat a
portion of the first channel 14a corresponding to the flow passage
resistor 302, the viscosity of the fluid is lowered by such heat,
and hence fluid flows through the first channel 14a. On the other
hand, when application of electric power to the heater 304 is
halted, to thereby cool the portion corresponding to the flow
passage resistor 302, the viscosity of the fluid is raised. As a
result, flow passage resistance is increased and flow of the fluid
is stopped. In other words, the valve section 300 functions whereby
fluid flow can be controlled by applying and halting application of
electric power to the heater 304.
[0146] As shown in FIG. 20, the second valve section 300B has a
vibration-generating section 310, which applies vibration to a part
of the first channel 14a. The vibration-generating section 310
comprises a vibration plate 312 provided on the first channel 14a,
and an operating section 314 (made up of a shape-retaining layer
316, an upper electrode 318, and a lower electrode 320) formed on
the vibration plate 312. When alternating voltage is applied to the
upper electrode 318 and the lower electrode 320, vibration is
easily generated in the first channel 14a.
[0147] The second valve section 300B utilizes change in flow
passage resistance caused by vibration. When vibration is applied
to a part of the first channel 14a, flow of fluid is stopped
because the flow passage resistance increases.
[0148] As shown in FIG. 21, the third valve section 300C comprises
a casing 332 provided on a lid plate 330 covering the first channel
14a, so that at least the first channel 14a is closed. A cavity
338, communicating with the first channel 14a via an inlet hole 334
and a discharge hole 336, is formed in the casing 332.
[0149] An operating section 340 (made up of a shape-retaining layer
342, an upper electrode 344, and a lower electrode 346) is formed
on the casing 332. The operating section 340 functions as an
actuator section 350, in conjunction with an upper portion
(vibration plate 348) of the casing 332.
[0150] Conversely to the pump section shown in FIG. 6, the inlet
hole 334 has a diameter that increases progressively toward the
cavity 338. The opening diameter on the side of the first channel
14a is smaller than the opening diameter on the side of the cavity
338. Similarly, the discharge hole 336 has a diameter that
decreases progressively toward the cavity 338. The opening diameter
on the side of the first channel 14a is larger than the opening
diameter on the side of the cavity 338. In other words, the inlet
hole 334 is structured so that pressure is easily applied via the
inlet hole 334 to fluid disposed upstream thereof by the fluid
contained in the cavity 338. The discharge hole 336 is structured
so that pressure is easily applied via the discharge hole 336 to
fluid contained in the cavity 338 by the fluid disposed downstream
of the discharge hole 336.
[0151] When the volume of the cavity 338 decreases by driving the
actuator section 350, and the sample is moved through the first
channel 14a by activating the pump section 22 shown in FIG. 18, a
force is exerted on the fluid in the cavity 338 to cause the fluid
to flow in an opposite direction (i.e., a direction opposite to the
flow of fluid caused by the pump section 22). As a result, flow of
fluid may be halted at the third valve section 300C.
[0152] The embodiments described above are illustrative of cases in
which two or three channels are merged, or in which two channels
intersect with each other. However, the present invention is also
applicable to cases in which four or more channels are merged, or
in which three or more channels intersect with each other.
[0153] It shall be understood that the microchemical chip according
to the present invention is not limited to the embodiments
described above, and that the invention may be embodied in other
various forms without departing from the gist or essential
characteristics of the present invention. For example, the
substrate 12 may be formed of zirconia ceramics, having low
reactivity with actuator materials, in the event that the pump
section 22 and the sample supply section 160 are formed integrally.
Alternatively, the substrate 12 may be composed of a zirconia
ceramic complex, in which only the plate member, for closing the
channel 14 at an upper surface thereof, is composed of glass.
INDUSTRIAL APPLICABILITY
[0154] As explained above, utilizing the microchemical chip
according to the present invention, it is possible to miniaturize
size of the chip, improve analytical accuracy of the sample, and to
analyze samples having no electrical charge. Further, use of
multiple channels can be facilitated.
[0155] Additionally, it is possible to improve analytical accuracy
and to realize high analysis speed, in combination with
electrophoresis.
* * * * *