Description
Title of Invention: MICROCHIP UNDER VACUUM
Technical Field
[0001] The present technology relates to a microchip. More specifically, the present
technology relates to a microchip for analyzing a substance contained in a solution or a
reaction product of the substance by introducing the solution into a region or regions
arranged in the microchip.
Background Art
[0002] In recent years, by application of the microfabrication technology in the semi
conductor industry, microchips have been developed in which channels or wells for
performing a chemical analysis or biological analysis are provided on a substrate made
of silicone or glass. The microchips can be employed to perform an analysis using
small amounts of samples, and allow disposable use (throwaway use) thereof. Ac
cordingly, the microchips are utilized especially for biological analyses in which a tiny
amount of a valuable sample or a large number of analytes are dealt with.
[0003] One example of application of the microchip is an optical detection system wherein a
substance is introduced into a plurality of regions arranged in the microchip and the
substance or a reaction product thereof is optically detected. Such type of optical
detection systems include an electrophoresis system wherein a plurality of substances
are separated by electrophoresis in channels in a microchip and the thus separated
substances are optically detected, and a reaction system (e.g., nucleic acid ampli
fication system) wherein reactions between a plurality of substances are allowed to
take place in wells in a microchip and the reaction products are optically detected.
[0004] The analysis conducted using a microchip has the following problems. Since the
samples are supplied in tiny amounts, it is difficult to introduce a sample solution into
the wells or channels. In addition, air present inside the wells or the like may cause the
introduction of a sample solution to be hampered or to take much time. Besides, at the
time of introducing the sample solution, bubbles may be generated inside the wells or
the like, whereby the amount of the sample solution introduced into the wells or the
like would be scattered, and the accuracy of analysis would be lowered. Further, in an
analysis involving heating of a sample, bubbles remaining inside the wells or the like
may be expanded to move the sample solution or to hinder the reaction. This would
lower the accuracy and efficiency of analysis.
[0005] In order to facilitate the introduction of a sample solution into a microchip, Patent
Literature (PTL) 1 discloses "a microchip wherein the inside of regions into which to
introduce a solution is set at a negative pressure in relation to an atmospheric
pressure." In this microchip, a sample solution is injected into the regions, whose
inside is set at the negative pressure, by use of a needle so that the sample solution is
sucked into the regions by the negative pressure. As a result, the introduction can be
achieved easily and in a short time.
Citation List
Patent Literature
[0006] [PTL1] JP 2011-163984A
Summary
Technical Problem
[0007] When the above-mentioned microchip is stored in the air for a long time, air may
permeate into the inside of the microchip to reduce the pressure difference between the
inside and the outside of the microchip. In such a case, a sufficient suction force for in
troduction of a sample solution may be lost. Accordingly, the present technology aims
at providing a microchip wherein the pressure inside the microchip can be checked
before introduction of a sample solution.
Solution to Problem
[0008] In order to solve the above-mentioned problem, according to the present technology,
there is provided
a microchip including a region of which the inside is set at a negative pressure in
relation to an atmospheric pressure, and a pressure indication section which presents an
air pressure state inside the region.
The region, preferably, includes a substrate layer having a self-sealing property based
on elastic deformation.
In addition, the pressure indication section may include the substrate layer.
The pressure indication section may include an elastic member which is filled with a
gas and is expanded or contracted according to a variation in an external pressure.
Besides, the pressure indication section may have a material whose color is changed
by a gas and/or a humidity change.
The pressure indication section may be provided at an outer surface of the microchip.
Further, the microchip may include a thermal history indication section which
presents a history of heat applied to the inside of the region.
According to the present technology, there is provided a microchip that is configured
to contain a sample solution for analysis. The microchip including a channel that is
maintained at a pressure level less than atmospheric pressure so as to allow flow of the
sample solution thru the channel; and a pressure indication section configured to detect
a change in the pressure level. A microchip apparatus and a method of manufacturing a
microchip are also provided.
Advantageous Effects of Invention
[0009] According to the present technology, there is provided a microchip having an in
dication section by which the pressure state inside the microchip can be visually
inspected.
Brief Description of Drawings
[0010] [fig. 1]Fig. 1 shows schematic views for illustrating the configuration of a microchip l a
according to a first embodiment of the present technology.
[fig.2]Fig. 2 shows schematic views for illustrating a method of introducing a sample
solution in the microchip la.
[fig.3]Fig. 3 shows views for illustrating a method of indicating a pressure state in a
pressure indication section 5 of the microchip la.
[fig.4]Fig. 4 is a schematic sectional view for illustrating the configuration of a
microchip lb according to a second embodiment of the present technology.
[fig.5]Fig. 5 is a schematic sectional view for illustrating the configuration of a
microchip l c according to a third embodiment of the present technology
[fig.6]Fig. 6 is a schematic sectional view for illustrating the configuration of a
microchip Id according to a fourth embodiment of the present technology.
[fig.7]Fig. 7 is a schematic sectional view for illustrating the configuration of a modi
fication of the microchip Id.
[fig.8]Fig. 8 shows schematic diagrams for illustrating a method of indicating a
thermal history in a thermal history indication section 6 of the microchip Id.
[fig.9]Fig. 9 shows schematic diagrams for illustrating a method of indicating a
thermal history on a real-time basis in the thermal history indication section 6 of the
microchip Id.
Description of Embodiments
[001 1] Now, preferred embodiments for carrying out the present technology will be
described below. Incidentally, the embodiments described below show representative
embodiments of the present technology, and the scope of the present technology is not
to be narrowly construed due to the embodiments. Description will be made in the
following order.
1. Microchip according to First Embodiment
(1) Configuration of microchip l a
(2) Method of introducing sample solution into microchip l a
(3) Indicating method at pressure indication section 5 of microchip l a
2. Microchip according to Second Embodiment
(1) Configuration of microchip lb
(2) Indicating method at pressure indication section 5 of microchip lb
3. Microchip according to Third Embodiment
4. Microchip according to Fourth Embodiment
(1) Configuration of microchip Id
(2) Configuration of microchip l e
(3) Indicating method at thermal history indication section 6
[0012] 1. Microchip according to First Embodiment
(1) Configuration of microchip l a
Fig. 1 shows schematic views for illustrating the configuration of a microchip l a
according to a first embodiment of the present technology. Fig. 1A is a schematic top
plan view, and Fig. IB is a schematic sectional view corresponding to P-P section of
Fig. 1A.
[0013] As shown in Fig. 1A, wells 41, 42, 43, 44, and 45 serving as analysis sites for a
substance contained in a sample solution or a reaction product of the substance are
disposed in the microchip la. Each of the wells communicates with an introduction
section 2 through a channel 31, 32, 33, 34, or 35. In addition, the microchip l a is
provided with a pressure indication section 5 in which a gas-filled body 5 1 is
contained. Incidentally, in the description of the microchip l a below, the five wells
supplied with the sample solution through the channel 31 will all be referred to as
wells 41. Similarly, the sets of five wells which are supplied with the sample solution
respectively through channels 32, 33, 34, and 35 will be referred to respectively as
wells 42, 43, 44, and 45.
[0014] The sample solution to be introduced into the microchip l a according to this em
bodiment refers to a solution containing an analyte or a substance which reacts with
another substance to produce an analyte. Examples of the analyte include nucleic acids
such as DNA, RNA, etc., peptides, and proteins inclusive of antibodies. In addition, a
biological sample that contains the analyte, such as blood, as it is or a diluted solution
thereof may be used as the sample solution to be introduced into the microchip la.
Besides, examples of the analytical technique in which the microchip l a is employed
include those analytical techniques in which a nucleic acid amplification reaction is
utilized, such as the conventional PCR (polymerase chain reaction) method in which a
temperature cycle is carried out or various isothermal amplification methods which
does not involve any temperature cycle.
[0015] The microchip l a is composed of three substrate layers 11, 12, and 13 (see Fig. IB).
As exemplified by the schematic sectional view in Fig. IB, the substrate layer 12 is
provided with the above-mentioned introduction section 2, channels 31, 32, 33, 34, and
35, and wells 41, 42, 43, 44, and 45. These regions in which the sample solution is
made to flow will be referred to as "reaction region R."
[0016] Besides, the substrate layer 12 is provided with a pressure indication section 5. The
pressure indication section 5 in the microchip according to the present technology
refers to a combination of a detection member or the like which shows a variation re
flecting a variation in the air pressure in the reaction region R with a vessel housing the
detection member or the like or with a material containing the detection member or the
like. The configuration of the pressure indication section 5 will be described in detail
in (2) below. In the microchip l a according to this embodiment, a gas-filled body 5 1 is
used as the detection member, and a part of the substrate layer 12 is configured as the
vessel which houses the gas-filled body 51. In the microchip la, the reaction region R
and the pressure indication section 5 do not communicate with each other but are
provided independently in the microchip la.
[0017] The substrate layer 13 is provided with an introduction port 2 1 for introducing the
sample solution into the microchip la. On the other hand, a surface opposite to the in
troduction port 2 1 of the substrate layer 11 is not provided with any opening part.
Therefore, the reaction region R in the microchip l a does not communicate with the
exterior.
[0018] As materials for the substrates 11, 12, and 13, there can be used glasses and various
plastics. Preferably, the substrate layer 11 is formed from an elastic material, whereas
the substrate layers 12 and 13 are each formed from a gas-impermeable material. With
the substrate layer 11 formed from an elastic material such as polydimethylsiloxane
(PDMS), the sample solution can be easily introduced into the introduction section 2
by a sample solution introducing method which will be described later. On the other
hand, with the substrate layers 12 and 13 each formed from a gas-impermeable
material such as polycarbonate (PC), it is possible to prevent the sample solution in
troduced into the wells 41, 42, 43, 44, and 45 from disappearing by permeating
through the substrate layer 11 when evaporated under heating (to prevent the solution
from being lost). Incidentally, in the case where the substance held in each well in the
microchip l a according to the present technology is optically analyzed, it is preferable
to select as material for each of the substrate layers a material which is lighttransmitting,
shows little autofluorescence, shows little wavelength dispersion and,
hence, induces little optical error.
[0019] Examples of the elastic material for the substrate layer include not only silicone
elastomers such as polydimethylsiloxane (PDMS) but also acrylic elastomers, urethane
elastomers, fluoro-elastomers, styrene elastomers, epoxy elastomers, and natural
rubber.
[0020] Examples of the gas-permeable material which can be adopted for forming the
substrate layers include glasses, plastics, metals, and ceramics. Examples of the
plastics include PMMA (polymethyl methacrylate; acrylic resin), PC (polycarbonate),
PS (polystyrene), PP (polypropylene), PE (polyethylene), PET (polyethylene
terephthalate), diethylene glycol bisallyl carbonate, SAN resin (styrene-acrylonitrile
copolymer), MS resin (MMA-styrene copolymer), TPX (poly(4-methylpentene-l)),
polyolefin, SiMA (siloxanyl methacrylate monomer) -MMA copolymer, SiMAfluorine-
containing monomer copolymer, silicone macromer-(A)-HFBuMA
(heptafluorobutyl methacrylate) -MMA ternary copolymer, and di-substituted polyacetylene
polymers. Examples of the metals include aluminum, copper, stainless steel
(SUS), silicon, titanium, and tungsten. Examples of the ceramics include alumina (Al2
0 3), aluminum nitride (A1N), silicon carbide (SiC), titanium oxide (Ti0 2), zirconia
oxide (Zr0 2), and quartz.
[0021] Fabrication of the introduction section 2, the channels 31, 32, 33, 34, and 35 and the
wells 41, 42, 43, 44, and 45 into the substrate layer 12 can be carried out by a known
technique. The known technique may be, for example, wet etching or dry etching of a
glass-made substrate layer, or nanoimprint, injection molding, or machining of a
plastic-made substrate layer. Besides, the introduction section 2 and the like may be
formed in the substrate layer 11.
[0022] Lamination of the substrate layers 11, 12, and 13 can be carried out by a known
method such as heat fusing, adhesive, anodic bonding, bonding by use of an adhesive
sheet, plasma activation bonding, and ultrasonic bonding. In addition, by carrying out
the lamination of the substrate layers 11, 12, and 13 under a negative pressure in
relation to an atmospheric pressure, it is possible to set the pressure inside the reaction
region R at a negative pressure (for example, 1/100 atm) in relation to the atmospheric
pressure. In the case where an elastic and gas-permeable material such as PDMS is
used for the substrate layer 11, letting the laminate of the substrate layers 11 and 12
stand under a negative pressure (vacuum) ensures that air in the reaction region R is
discharged by permeation through the substrate 11, so that the inside of the reaction
region R can be set at a negative pressure (vacuum) in relation to the atmospheric
pressure. Besides, in the microchip la, the inside of the pressure indication section 5
housing the gas-filled body 5 1 can also be set at a negative pressure in relation to the
atmospheric pressure, like the reaction region R.
[0023] (2) Method of introducing sample solution into microchip l a
Where the substrate layer 11 formed of an elastic material is used in the microchip
la, the sample solution can be introduced into the microchip l a by use of, for example,
a syringe which can be fitted with a needle or the like at the tip thereof. Fig. 2A and
Fig. 2B are views which, by enlarging the vicinity of the introduction section 2 shown
in Fig. IB, illustrates a method of introducing a sample solution into the microchip la.
[0024] In introducing a sample solution, first, the tip of a needle N attached to a syringe
filled with the sample solution is made to pass through the introduction port 2 1 and
pierce through the substrate layer 11 (see Fig. 2A). When a part of the needle N
reaches the introduction section 2, a pressure difference between the inside of the
microchip l a and the outside of the microchip l a (the inside of the syringe) causes the
sample solution in the syringe to pass through the lumen of the needle N and be sucked
into the introduction section 2. The sample solution thus introduced into the in
troduction section 2 flows through the channel 33, to reach the well 43 serving as an
analysis site (the well 43 is not shown). In this way, with the inside of the reaction
region R set at a negative pressure in relation to the atmospheric pressure and sealed
off by the substrate layer formed of a pierceable material, the sample solution can be
easily introduced into the microchip la.
[0025] After the introduction of the sample solution, the needle N is pulled off from the
microchip l a (see arrow Y in Fig. 2B). In this instance, if the substrate layer 11 is
formed from a material which has a self-sealing property based on elastic deformation,
a through-hole P formed in the substrate layer 11 due to the piercing by the needle N
can be spontaneously sealed off by elastic deformation of the substrate layer 11. In the
present technology, the spontaneous sealing-off of the through-hole P by elastic de
formation of the substrate layer 1 1 is defined as the "self-sealing property" of the
substrate layer. With the through-hole P thus sealed off, mixing of air into the reaction
region R in the microchip l a is prevented from occurring.
[0026] (3) Indicating method at pressure indication section 5 of microchip l a
As above-described, the inside of the microchip l a can be set at a negative pressure
in relation to the atmospheric pressure by, for example, laminating the substrate layers
11, 12, and 13 under a negative pressure. However, because of the introduction of the
sample solution by piercing or for the like reason, it is difficult to cover entirely the
outer surfaces of the microchip l a with the substrate layers 12 and 13 formed of gasimpermeable
material; hence, the substrate layer 11 is exposed to the outside, at the in
troduction port 2 1 and a side surface S (see Fig. IB). Therefore, storage of the
produced microchip l a under the atmospheric pressure may result in that air permeates
through the substrate layer 11 into the reaction region R of the microchip la, and the
air pressure inside the microchip l a rises with the lapse of time, making it impossible
to obtain a sufficient suction force for introducing the sample solution. In view of this,
the microchip l a is provided with a pressure indication section 5 for presenting an air
pressure state, reflecting such a variation in the air pressure inside the reaction region
R. Referring to Fig. 3A and Fig. 3B, the pressure indication section 5 will be described
in detail below.
[0027] Fig. 3A and Fig. 3B are schematic top plan views of the microchip la. Fig. 3A shows
the state of the pressure indication section 5 when the reaction region R in the
microchip l a is set at a negative pressure in relation to the atmospheric pressure. In the
pressure indication section 5 is housed a gas-filled body 5 1 as a detection member
which varies reflecting a variation in the air pressure inside the reaction region R. The
gas-filled body 51 is an elastic member of natural rubber or a synthetic rubber or the
like which is filled with a gas such as air or nitrogen. In addition, a part of the gasfilled
body 5 1 may be fixed to a pressure indication section bottom surface 52 (see Fig.
IB). The gas-filled body 5 1 is filled with a gas in such a manner that the gas-filled
body 51 has a sufficient volume for covering the pressure indication section bottom
surface 52 in the condition where the reaction region R is at a negative pressure in
relation to the atmospheric pressure.
[0028] Fig. 3B shows a state wherein air has permeated into the reaction region R of the
microchip l a and the air pressure inside the reaction region R has approached the at
mospheric pressure. The permeation of air into the reaction region R takes place
through the substrate layer 11. Therefore, air permeates also into the pressure in
dication section 5, which is partly sealed with the substrate layer 11 as shown in Fig.
IB, similarly to the permeation into the reaction region R. Upon permeation of air into
the pressure indication section 5, the air pressure in the surroundings of the gas-filled
body 5 1 rises. In the condition where the reaction region R and the pressure indication
section 5 are each at a negative pressure in relation to the atmospheric pressure,
therefore, the gas-filled body 5 1 having been covering the pressure indication section
bottom surface 52 is contracted (see Fig. 3B), due to a reduction in the volume of the
gas confined in the gas-filled body 51, according to the pressure difference between the
inside of the gas-filled body 5 1 and the surroundings. This contraction of the gas-filled
body 5 1 reflects the variation in the air pressure in the pressure indication section 5.
The reaction region R and the pressure indication section 5 are both configured to
include the air-permeable substrate layer 11 at least at a part thereof. Therefore, the
reduction in the volume of the gas-filled body 5 1 reflects also the variation in the air
pressure inside the reaction region R due to the air having permeated thereinto through
the substrate layer 11, like into the pressure indication section 5.
[0029] In the case where the substrate layers 11, 12, and 13 constituting the microchip l a are
each formed from a light-transmitting material, the gas-filled body 5 1 housed in the
pressure indication section 5 and the pressure indication section bottom surface 52 can
be visually checked from outside of the microchip la. For instance, as shown in Fig.
3B, a reference line 53 is preliminarily drawn on the pressure indication section bottom
surface 52. The reference line 53 cannot be visually confirmed since it is covered with
the gas-filled body 51 in the condition where the reaction region R is at a negative
pressure in relation to the atmospheric pressure and a sufficient pressure difference for
introduction of a sample solution exists between the inside and the outside of the
microchip la, as shown in Fig. 3A. On the other hand, when the air pressure inside the
reaction region R is raised to a state unsuited to introduction of the sample solution and
the gas-filled body 5 1 is contracted, as shown in Fig. 3B, the reference line 53 appears.
In this manner, the variation in the air pressure inside the reaction region R is reflected
on, and the air pressure state in the reaction region R is presented by, the pressure in
dication section 5 in the microchip la. The air pressure state indicated by the pressure
indication section 5 is, in other words, the degree of maintenance of negative pressure
inside the reaction region R of the microchip la.
[0030] The method in which the reference line 53 is provided on the pressure indication
section bottom surface 52 is not restrictive, and other methods may also be adopted.
For example, the gas-filled body 5 1 may be colored and the volume of the gas-filled
body 51 may be visually confirmed, to use the checked volume as an indication or
estimate of the air pressure inside the reaction region R. In addition, characters such as
"UNUSABLE" may be printed on the pressure indication section bottom surface 52, to
be used as a substitute for the reference line 53. A yardstick for the size and position of
the reference line 53 or characters drawn on the pressure indication section bottom
surface 52, or for the volume of the gas-filled body 51, may be determined by pre
liminarily calculating the correlation between the air pressure inside the reaction region
R and the volume of the gas-filled body 51.
[0031] The position in the microchip l a where to dispose the pressure indication section 5 is
not restricted to the position shown in Fig. 1A and Fig. IB. It suffices that the pressure
indication section 5 is provided in the microchip l a and that at least one surface thereof
is composed of a substrate layer formed of an elastic material, such as the substrate
layer 11. Since the substrate layer 11, serving as a route through which air permeates
into the reaction region R, is provided also for the pressure indication section 5, the
quantity of air permeating into the pressure indication section 5 is approximate to the
quantity of air permeating into the reaction region R. Therefore, the variation in the
volume of the gas-filled body 51 in the pressure indication section 5 reflects the air
pressure inside the reaction region R.
[0032] Incidentally, the pressure indication section 5 provided in the microchip l a can be
used as a yardstick for judging the air pressure inside the reaction region R, also in the
case where the microchip l a in which the pressure difference between the inside and
the outside thereof is reduced due to permeation of air into the reaction region R is
stored under a negative pressure so that the microchip l a is again deaerated to a state in
which a sample solution can be introduced thereinto.
[0033] In the microchip l a according to this embodiment, the pressure indication section 5
of which at least one surface is composed of an elastic substrate layer, like the reaction
region R, is provided, whereby it is ensured that a variation approximate to the
pressure variation generated by permeation of air into the reaction region R is
generated also in the pressure indication section 5. Therefore, the pressure indication
section 5 reflects the state of gas pressure inside the reaction region R, so that the air
pressure state inside the region R can be visually checked through the pressure in
dication section 5. In the microchip la, the air pressure inside the reaction region R can
be easily known by the pressure indication section 5, so that it is possible to judge
whether the microchip l a is fit for performing analysis thereby. Since the state of the
microchip l a can be confirmed before introduction of a sample solution, erroneous
consumption of a valuable sample can be prevented from occurring.
[0034] 2. Microchip according to Second Embodiment
(1) Configuration of microchip lb
Fig. 4 is a schematic sectional view for illustrating the configuration of a microchip
lb according to a second embodiment of the present technology. The microchip lb is
the same in configuration as that in the first embodiment, except for the position where
a pressure indication section 5 is disposed and a detection member housed in the
pressure indication section 5. The same configurations as those in the first embodiment
are denoted by the same reference signs as used above, and descriptions of them will
be omitted. In addition, the materials of substrate layers 11, 12, and 13 constituting the
microchip lb are the same as those of the substrate layers of the microchip l a which
have been denoted by the same reference signs.
[0035] The pressure indication section 5 in the microchip lb is provided on the substrate
layer 13, and constitutes an outer surface of the microchip lb. In the pressure in
dication section 5 is housed a detection material 54, in place of the gas-filled body 51
described in the first embodiment above. The detection material 54 is a material whose
color changes through reaction with a gas, such as oxygen, or in response to humidity.
As the detection material 54, there can be used, for example, leuco dyes which show a
color change when oxidized and silica gel or the like which shows a color change
through moisture absorption. Besides, these detection materials 54 may be kneaded
into a synthetic resin or the like which is then firmly attached to an outer surface of the
microchip lb, or may be applied to a film or the like which is then adhered to an outer
surface of the microchip lb. Alternatively, the detection material 54 may be contained
in a vessel made of an air-permeable and light-transmitting synthetic resin or the like,
the vessel being firmly attached to an outer surface of the microchip lb.
[0036] (2) Indicating method at pressure indication section 5 of microchip lb
The microchip lb is so configured that the reaction region R is set at a negative
pressure in relation to the atmospheric pressure, for example by laminating the
substrate layers 11, 12, and 13 under a negative pressure in relation to the atmospheric
pressure. When the microchip lb in this state is kept in a preserving vessel formed of a
metal or the like material, the airtightness of the reaction region R can be easily
maintained. When the preserving vessel is placed in the atmospheric air, however, penetration
of air into the preserving vessel proceeds gradually, so that air soon permeates
also into the inside of the microchip lb. In view of this, the microchip lb is provided
with the pressure indication section 5 by which air permeating into the preserving
vessel or moisture is detected. An indicating method at the pressure indication section
5 wherein a variation in the air pressure inside the reaction region R of the microchip
lb is reflected, and the state of the air pressure is presented, by use of the detection
material 54 will be described below. The following description will be made based on
an exemplary case where an oxidation-reduction coloring matter is used as the
detection material 54.
[0037] The oxidation-reduction coloring matter contains a coloring matter which shows a
color change upon undergoing an oxidation reaction. When air penetrates into the
preserving vessel and reaches the pressure indication section 5, therefore, the
oxidation-reduction coloring matter contained in the detection material 54 shows a
change in color. On the other hand, the oxidation-reduction coloring matter contains a
reducing agent, as well. This ensures that in an deaerated condition, the oxidation
reaction of the coloring matter stops, and due to the function of the internally present
reducing agent, the coloring matter shows a color corresponding to the reduced state.
The detection material 54 is housed in the pressure indication section 5, and a change
in color of the detection material 54 can be visually confirmed from outside of the
microchip lb. Therefore, by checking the change in color at the pressure indication
section 5 upon taking out the microchip lb from the preserving vessel, it is possible to
judge a change in the air pressure inside the microchip.
[0038] The pressure indication section 5 of the microchip lb shows a change through
reaction with air in the outside of the microchip lb, unlike the pressure indication
section 5 provided in the first embodiment. Since the microchip lb is stored in the
preserving vessel, however, the air permeating into the inside of the microchip lb is
first the air that has penetrated into the preserving vessel. The detection of air in the
preserving vessel reflects the permeation of air into the reaction region R of the
microchip lb. The correlation between a variation in color at the detection material 54
and the air pressure inside the reaction region R of the microchip lb is preliminarily
calculated. By this it is ensured that the pressure indication section 5 of the microchip
lb reflects the variation in the air pressure inside the reaction region R, and can present
the state of gas pressure in the reaction region R. Incidentally, characters such as
"UNUSABLE" may be provided, by printing or the like, on the pressure indication
section 5 by use of the oxidation-reduction coloring matter. By such a method as this,
the degree of negative pressure inside the reaction region R may be presented on the
pressure indication section 5 by, for example, the appearance of the characters in place
of the color change.
[0039] The position in the microchip lb at which the above-mentioned pressure indication
section 5 is disposed is not restricted to the position shown in Fig. 4. Preferably, the
pressure indication section 5 is provided in or on the substrate layers constituting the
microchip outer surface, such as the substrate layers 12 and 13, in such a manner as to
be exposed to the outside of the microchip lb. With the pressure indication section 5
provided in such a position, it is possible by the pressure indication section 5 to detect
penetration of air into the preserving vessel in which the microchip lb is housed.
[0040] When the microchip lb according to this embodiment is taken out of the preserving
vessel after stored in the preserving vessel, it is possible by checking the pressure in
dication section 5 to judge whether the air pressure inside the reaction region R is a
negative pressure in relation to the atmospheric pressure to such an extent as to enable
introduction of a sample solution. Accordingly, the degree of maintenance of negative
pressure inside the microchip lb can be checked before introduction of a sample
solution, so that erroneous consumption of valuable samples can be obviated.
[0041] 3. Microchip according to Third Embodiment
Fig. 5 is a schematic sectional view illustrating the configuration of a microchip l c
according to a third embodiment of the present technology. The microchip l c is the
same in configuration as those in the first and second embodiments, except for the
position where a pressure indication section 5 is disposed. The same configurations as
those in the first and second embodiments are denoted by the same reference signs as
used above, and descriptions of them will be omitted. Besides, the materials of
substrate layers 11, 12, and 13 constituting the microchip l c are the same as those of
the substrate layers of the microchip l a which have been denoted by the same
reference signs.
[0042] As shown in Fig. 5, the microchip l c is provided with the pressure indication
sections 5 in two locations. One of the pressure indication sections 5 is located
between the substrate layer 11 which is elastic and the substrate layer 12 constituting
an outer surface of the microchip lc. Namely, this pressure indication section 5 is
provided at the same position as the pressure indication section 5 described in the first
embodiment above. In the pressure indication section 5 thus provided inside the
microchip lc, a detection material 54 is contained, which shows a change in color
through reaction with air, like the detection material 54 in the pressure indication
section 5 described in the second embodiment above.
[0043] On the other hand, the other of the pressure indication sections 5 is provided in the
substrate layer 13, and constitutes an outer surface of the microchip lc. Namely, this
pressure indication section 5 is provided in the same position as the pressure indication
section 5 described in the second embodiment above. In this pressure indication
section 5 is housed a gas-filled body 51. The volume of the gas-filled body 5 1 varies
with a variation in the surrounding pressure, in the same manner as in the pressure in
dication section 5 described in the first embodiment.
[0044] The member and the material housed in the pressure indication sections 5 at the two
locations and operative to sense a pressure variation or air are not restricted to the com
bination shown in Fig. 5; the member and the material may both be gas-filled bodies
51 or may both be detection materials 54. Further, a configuration may be adopted
wherein the detection material 54 is contained in the pressure indication section 5
provided at the outside of the microchip lc, and the gas-filled body 5 1 is housed in the
pressure indication section 5 provided inside the microchip lc.
[0045] The positions where the two pressure indication sections 5 are disposed are not
limited to the positions shown in Fig. 5, in the microchip lc. Preferably, the positions
are the locations where the pressure indication sections 5 are disposed in the inside of
and at the outside of the microchip lc, as described in the first and second em
bodiments. Besides, in the microchip l c in this embodiment, the number of the
pressure indication sections 5 disposed is not limited.
[0046] In the microchip l c according to this embodiment, the pressure indication sections 5
are provided in the two locations, one inside and one outside. This ensures that whether
the air pressure inside the reaction region R is in a sufficient range for introduction of a
sample solution can be easily judged before introduction of the sample solution, both
in the case where the microchip l c is stored under an atmospheric pressure and in the
case where the microchip l c is stored in a preserving vessel.
[0047] 4. Microchip according to Fourth Embodiment
(1) Configuration of microchip Id
Fig. 6 is a schematic sectional view illustrating the configuration of a microchip Id
according to a fourth embodiment of the present technology. The microchip Id is the
same in configuration as that in the first embodiment, except that a thermal history in
dication section 6 is provided. The same configurations as those in the first em
bodiment are denoted by the same reference signs as used above, and descriptions of
them will be omitted. Besides, the materials for substrate layers 11, 12, and 13 con
stituting the microchip Id are the same as those for the substrate layers in the
microchip l a which are denoted by the same reference signs.
[0048] As shown in Fig. 6, the thermal history indication section 6 of the microchip Id is
provided on the substrate layer 13, and constitutes an outer surface of the microchip
Id. The thermal history indication section 6 has a detection material 6 1 by which a
temperature variation such as heating or cooling is detected. Examples of the material
by which temperature variations are sensed include leuco dyes capable of showing
color changes through oxidation-reduction reactions, which will be described later.
Other examples include pyrolysis of metallic salts, crystal transition of metal
complexes, and variations in molecular orientation of liquid crystals. These show color
changes in response to temperature variations and, hence, can be utilized as the
detection material 61.
[0049] The detection material 6 1 may be housed in a vessel formed of a synthetic resin or
the like and provided on an outer surface of the microchip Id. Alternatively, the
detection material may be kneaded into other material or applied to a surface of a film
or the like, before being provided on a surface of the microchip Id. Or, the detection
material 6 1 may be provided on an outer surface of the microchip Id by use of an ink
jet system.
[0050] In the case where the microchip Id is used for an analysis which involves a heating
procedure such as PCR, the coloring matter or the like contained in the detection
material 6 1 at the thermal history indication section 6 shows a change in color,
whereby a thermal history of the microchip Id having been placed in a heated state is
indicated. Where the microchip Id is heated, a heating system for heating the
microchip Id by holding the microchip Id from the directions orthogonal to the
substrate layers 11, 12, and 13 may be employed, for evenly heating wells 43 and the
like provided inside the microchip Id. In this case, the thermal history indication
section 6 and the heating system make contact with each other. When a heater
provided with a rugged pattern is disposed at that surface of the heating system which
makes contact with the thermal history indication section 6, only the projected portions
of the rugged pattern make contact with the thermal history indication section 6. Con
sequently, only the portions of the thermal history indication section 6 which are
contacted by the projected portions show a change in hue. In this manner, the thermal
history indication section 6 may be provided with characters such as letters, numerals,
marks, etc., symbols, a one-dimensional or two-dimensional bar code symbol, patterns,
or the like, by utilizing a heater of a heating system.
[0051] The number of the thermal history indication section(s) 6 provided on the microchip
Id is not limited. A plurality of thermal history indication sections 6 may be provided
at different positions on the surface of the microchip Id, whereby it is possible to
check whether heating of the microchip Id is conducted uniformly.
[0052] (2) Configuration of microchip l e
Fig. 7 is a schematic sectional view illustrating the configuration of the microchip l e
which is a modification of the microchip Id. The microchip l e is the same in con
figuration as the microchip Id, except for the position where a thermal history in
dication section 6 is disposed. The same configurations as those of the microchip Id
are denoted by the same reference signs as used above, and descriptions of them will
be omitted. In addition, the materials for substrate layers 11, 12, and 13 constituting the
microchip l e are the same as those for the substrate layers in the microchip l a which
are denoted by the same symbols.
[0053] In the microchip l e shown in Fig. 7, the thermal history indication section 6 is
provided in the same substrate layer 12 as that in which wells as analysis sites for a
sample solution introduced into the microchips Id are provided. The thermal history
indication section 6 has a detection material 6 1 such as a leuco dye which shows a
change in color in response to a change in temperature, such as heating or cooling. A
part of the substrate layer 12 is configured as a vessel in which to contain the detection
material 61. Therefore, the thermal history indication section 6 in the microchip l e can
indicates a thermal history, reflecting the temperature variations in the analysis sites
such as the wells 43.
[0054] The position where the thermal history indication section 6 is disposed is not re
stricted to the position shown in Fig. 7. It is preferable, however, to provide the
thermal history indication section 6 in the same substrate layer 12 as that in which the
wells 43 and the like are provided as analysis sites for an analyte contained in a sample
solution, and in proximity to the wells 43. Incidentally, the thermal history in the
present technology is defined as including not only a thermal history such as the
presence/absence of heating, the number of times of heating, etc. but also a tem
perature condition of the microchip l e on a real-time basis.
[0055] The detection material 6 1 contained in the thermal history indication section 6
provided in the microchip l e may be a plurality of coloring matters different in
response temperature, and the plurality of coloring matters may be aligned in the
thermal history indication section 6 or mixed with each other. Microencapsulation of
the detection material 6 1 facilitate mixing of multiple kinds of detection materials 61.
For instance, a coloring matter which shows a change in hue to red at a temperature of
5 deg C or above and a coloring matter which shows a change in hue to black at a tem
perature of 40 deg C or above may be mixed with each other. This ensures that when
the thermal history indication section 6 is preserved at low temperature, it is colorless,
so that the preserved state of the microchip l e can be confirmed. When the thermal
history indication section 6 turns red, it can be confirmed that the microchip l e has
reached room temperature. Further, when the microchip l e is treated by a heating
system and the thermal history indication section 6 turns black, it can be confirmed
that the temperature of the microchip l e has been raised. For instance, where a step of
heating the microchip l e to 60 deg C is employed for an analysis, the response tem
perature of the coloring matter provided as the detection material 6 1 may be designed
and prepared in the range from room temperature to 60 deg C. This ensures that even
where it is unclear whether or not the microchip l e has been heated, it can be dis
tinguished by visual inspection of the color of the coloring matter that the microchip l e
is a used one.
[0056] The change in color of the detection material 6 1 in the thermal history indication
section 6 may be judged by visual inspection. Besides, another configuration may be
adopted wherein the color in hue is digitized by use of a spectrophotometer or the like
provided in an optical analyzing system, to be indicated as a temperature value or in
the form of a word such as "USED" obtained by appropriate conversion.
[0057] (3) Indicating method at thermal history indication section 6
A method of presenting a thermal history by sensing an internal temperature
variation, in the thermal history indication section 6 in the microchip Id or its modi
fication, the microchip le, will be described in detail below, taking a leuco dye L as an
example and referring to Figs. 8 and 9. Figs. 8 and 9 schematically illustrate the
detection material 6 1 contained in the thermal history indication section 6.
[0058] The leuco dye L shows a change in hue when oxidized. Therefore, a reagent for
oxidizing the leuco dye L is used as a developer D, together with the leuco dye L. Fig.
8A shows a state of the microchip Id, l e before heating. The leuco dye L and the
developer D are held in the state of being contained and dispersed in a phase transition
material B (binder) which is in a solidified state. Fig. 8B shows a state of the microchip
Id, l e after heating. When the phase transition material B is brought to a phase
transition temperature by heating, a phase transition takes place; specifically, the phase
transition material B having been solid melts. As a result, it becomes easy for the leuco
dye L and the developer D contained in the phase transition material B to be coupled
together. By coupling with the developer D, the leuco dye L is oxidized, to show a
change in hue. Fig. 8C shows a state of the microchip Id, l e cooled again to normal
temperature after the heating in Fig. 8B. The phase transition material B is again so
lidified, whereby separation of the leuco dye L and the developer D from each other is
hindered, so that the hue of the leuco dye L is the same as that upon the heating.
[0059] As shown in Fig. 8A to Fig. 8C, the material containing the leuco dye L is housed in
the thermal history indication section 6, whereby it can be checked, at the time of
heating and after heating, whether the microchip Id, l e is a used one or not.
[0060] Examples of the leuco dye L include crystal violet
([4-{bis(4-dimethylaminophenyl)methylene}-2,5-cyclohexadien-l-ylidene]dimethylam
monium chloride). Crystal violet undergoes cleavage of a lactone ring by a solid acidic
substance, is thereby protonated, and turns violet from a colorless state. Other
examples of the leuco dye having a lactone ring include phenolphthalein and thymolphthalein.
The phenolphthalein appears colorless in a neutral condition and red in a
basic condition, whereas thymolphthalein appears colorless in a neutral condition and
blue in a basic condition.
[0061] In addition, examples of the developer D include solid acidic substances which
develop the leuco dye. Specific examples of the developer D include bisphenol A
(2,2-bis(p-hydroxyphenyl)propane). Examples of the phase transition material B
include dibutylphenol (2,6-di-tert-butylphenol).
[0062] It suffices for the phase transition material B or the like to be selected from those
having an appropriate phase transition temperature, according to the method in which
the microchip Id, l e is to be used. Examples of the phase transition material B include
dibutylphenol (2,6-di-tert-butylphenol). The phase transition temperature of the phase
transition material B can be changed by selection of the component materials. Since
the phase transition material B melts at or above its phase transition temperature, the
response temperature of the detection material 6 1 can be controlled thereby.
Specifically, by selecting the kind of the phase transition material B, the leuco dye L
and the developer D can be solidified in a mutually coupled state, and may also be so
lidified in a dispersed (mutually separated) state.
[0063] For instance, a coloring matter to be used for the detection material 6 1 can be
prepared by a method in which crystal violet and bisphenol A in reduced states are
dispersely mixed into a melt of dibutylphenol, the resulting mixture is applied to a
substrate, and the mixture is solidified by cooling. Since dibutylphenol has a melting
point of 35 to 38 deg C, heating to 40 deg C causes the prepared solidified matter to
melt. This results in that crystal violet and bisphenol A interact, and crystal violet is
oxidized, to be developed. Cooling this system causes crystal violet to be kept in the
oxidized state, whereby the developed color is preserved.
[0064] Fig. 8D shows the detection material 6 1 in a state wherein the leuco dye L and the
developer D has preliminarily been coupled together. Fig. 8E shows a state after
heating of the microchip Id, le. When the phase transition material B is brought to the
phase transition temperature by heating, a phase transition takes place; specifically, the
phase transition material B having been solid melts. Where the phase transition
material B has been solidified with the leuco dye L and the developer D in the coupled
state, the heating facilitates separation of the leuco dye L and the developer D from
each other. Upon the separation, the action of the developer D is weakened, and the
leuco dye L is brought into the reduced state. When cooled after the heating, the leuco
dye L and the developer D are fixed in a state similar to the state upon heating, so that
an undeveloped state of the leuco dye L is maintained (Fig. 8F).
[0065] On the other hand, by using a developer D having a melting point higher than the
phase transition temperature of the phase transition material B, it is also possible to reversibly
indicate changes in hue of the leuco dye L. Fig. 9A shows a state of the
microchip Id, l e before heating. The leuco dye L and a crystallized developer D are
contained in the phase transition material B being in a solidified state, and are kept in a
dispersed state. Fig. 9B shows a state after heating of the microchip Id, le. When tem
perature is raised to the melting point of the developer D, the phase transition material
B having been solid melts, and the developer D having been crystallized also melts, to
become able to couple with the leuco dye L. As a result, the leuco dye L is oxidized,
producing a change in hue. Fig. 9C shows a state of the microchip Id cooled again to
normal temperature after the heating in Fig. 9B. In the cooling process, the developer
D is first recrystallized, to loose its interaction with the leuco dye L, whereby the hue
of the leuco dye L is again changed. Thereafter, the phase transition material B is so
lidified.
[0066] As the phase transition material B, for example, there may be used a cellulose to
which a hydrophobic residual group such as a long chain alkyl group has been linked.
The phase transition material B can be brought into transition between a hydrophilic
state and a hydrophobic state at the phase transition temperature. At temperatures
higher than the phase transition temperature, the phase transition material B melts,
whereby the cellulose is loosened, to generate a hydrophilic environment for the leuco
dye L and the developer D, resulting in a change in color. At low temperatures, the
cellulose crystallizes, whereby a hydrophobic environment is generated in the phase
transition material B under the action of the hydrophobic residual groups. In this
instance, the interaction between the leuco dye L and the developer D is lost, resulting
in a reversible change in color.
[0067] It is also possible to achieve reversible changes in color, by admixing the detection
material 6 1 with a decolorizing agent Q. As shown in Fig. 9D, the leuco dye L and the
developer D are kept coupled together at temperatures lower than the phase transition
temperature of the phase transition material B. At temperatures higher than the phase
transition temperature, the decolorizing agent Q in a dispersed state causes dispersion
of the leuco dye L and the developer D, thereby producing a change in color (Fig. 9E).
Thereafter, when temperature is again set below the phase transition temperature, the
decolorizing agent Q is crystallized, so that the leuco dye L and the developer D are
again coupled with each other, producing a reversible change in color (Fig. 9F).
Known examples of the decolorizing agent Q include organic matters
(R-CH=N-R',where R and R'are various organic groups) having an azomethine link.
[0068] When a material containing the leuco dye L capable of reversible changes in hue is
housed in the thermal history indication section 6, as shown in Fig. 9, temperature
changes inside the microchip Id, l e can also be visually confirmed on a real-time
basis.
[0069] For inducing a change in color at the thermal history indication section 6, a pressure
exerted on the microchip Id, l e by the heating system, for example, may also be used,
other than the heating. For instance, a thermal history indication section 6 wherein mi
crocapsules filled with a leuco dye and microcapsules filled with a developer D are
arranged in an aligned manner is provided at an outer surface of the microchip Id. In
this case, application of a pressure causes breakage of the two kinds of microcapsules
in the thermal history indication section 6, whereby the leuco dye L and the developer
D are mixed with each other, producing a change in color.
[0070] In the microchip Id according to this embodiment and its modification, the
microchip le, it is possible to confirm a thermal history in addition to the abovementioned
change in the pressure inside the microchip. Since the microchip produced
by processing substrate layers and the like has a fine internal structure, the sample
solution introduced into the microchip is difficult to inspect visually. In the microchip
Id, le, the presence of the thermal history indication section 6 makes it possible to
easily judge whether the microchip is a used one or not. Furthermore, where the
thermal history section 6 is provided in the same substrate layer as that provided with
the wells 43 and the like, it is also possible to check the temperature variations in the
analysis sites on a real-time basis.
[0071] Incidentally, the microchip in which to provide the thermal history indication section
6 is not restricted to a microchip whose inside is set to a negative pressure in relation to
the atmospheric pressure. The thermal history indication section 6 may be provided in
a microchip such that the pressure inside the microchip and the pressure outside the
microchip are equal.
[0072] The present technology may assume the following configurations.
(1) A microchip including a region of which the inside is set at a negative pressure in
relation to an atmospheric pressure, and a pressure indication section which presents an
air pressure state inside the region.
(2) The microchip as described in the above paragraph (1), wherein the region
includes a substrate layer having a self-sealing property based on elastic deformation.
(3) The microchip as described in the above paragraph (2), wherein the pressure in
dication section includes the substrate layer.
(4) The microchip as described in any of the above paragraphs (1) to (3), wherein the
pressure indication section includes an elastic member which is filled with a gas and is
expanded or contracted according to a variation in an external pressure.
(5) The microchip as described in any of the above paragraphs (1) to (3), wherein the
pressure indication section has a material whose color is changed by a gas and/or a
humidity change.
(6) The microchip as described in the above paragraph (1) or (2), wherein the
pressure indication section is provided at an outer surface of the microchip.
(7) The microchip as described in any of the above paragraphs (1) to (6), including a
thermal history indication section which presents a history of heat applied to the inside
of the region.
(8) A microchip configured to contain a sample solution for analysis, the microchip
comprising:
a channel that is maintained at a pressure level less than atmospheric pressure so as to
allow flow of the sample solution thru the channel; and
a pressure indication section configured to detect a change in the pressure level.
(9) The microchip as described in (8), further comprising a substrate layer including a
self-sealing material configured to allow introduction of the sample solution into the
microchip.
(10) The microchip as described in (9), wherein at least a portion of the pressure in
dication section contacting with the self-sealing material.
(11) The microchip as described in (10), wherein the pressure indication section is p o
sitioned on an inner surface of the microchip.
(12) The microchip as described in (9), further comprising a second substrate layer
including the pressure indication section and the channel.
(13)The microchip as described in (8), wherein the pressure indication section includes
a material that detects gas or humidity associated with the change in pressure level.
(14) The microchip as described in (8), wherein the pressure indication section
includes an elastic material configured to respond to the change in the pressure level.
(15) The microchip as described in (14), further comprising a reference line.
(16) The microchip as described in (15), further comprising a plurality of pressure in
dication sections configured to detect the change in the pressure level.
(17) The microchip as described in (16) wherein a first pressure indication section
includes an elastic material configured to respond to the change in the pressure level,
and wherein a second pressure indication section is configured to detect gas or
humidity associated with the change in pressure level.
(18) The microchip as described in (17), wherein the first pressure indication section is
positioned on an inner surface of the microchip and the second pressure indication
section is positioned on an outer surface of the microchip.
(19) The microchip as described in (17), wherein the first pressure indication section is
positioned on an outer surface of the microchip and the second pressure indication
section is positioned on an inner surface of the microchip.
(20) The microchip as described in (8), wherein the pressure indication section is p o
sitioned on at least one of an inner surface and an outer surface of the microchip.
(21) The microchip as described in (8), further comprising a thermal history indication
section configured to detect a temperature change associated with the microchip.
(22) The microchip as described in (21), wherein the thermal history indication section
is positioned on an inner surface of the microchip.
(23) The microchip as described in (22), wherein the pressure indication section is p o
sitioned on an inner surface of the microchip.
(24) The microchip as described in (21), wherein the thermal history indication section
is positioned on an outer surface of the microchip.
(25) The microchip as described in (8), further comprising a well in communication
with the channel, wherein the well is configured to serve as an analysis site.
(26) The microchip as described in (25), further comprising a plurality of channels in
communication with one or more wells.
(27) A microchip apparatus comprising a microchip configured to contain a sample
solution for analysis, wherein the microchip includes a channel that is maintained at a
pressure level less than atmospheric pressure so as to allow flow of the sample solution
thru the channel; and a pressure indication section configured to detect a change in the
pressure level.
(28) A method of manufacturing a microchip configured to contain a sample solution
for analysis, the method comprising providing the microchip including a channel
maintained at a pressure level less than atmospheric pressure so as to allow flow of the
sample solution thru the channel, and the microchip including a pressure indication
section configured to detect a change in the pressure level.
Industrial Applicability
[0073] The microchip pertaining to the present technology ensures that the pressure state
inside the microchip can be easily checked before introduction of a sample solution.
Therefore, the microchip pertaining to the present technology is suitably applicable, for
example, to an analysis which involves a heating procedure while using a tiny amount
of sample, such as a nucleic acid amplification reaction.
Reference Signs List
[0074] B: Phase transition material; D: Developer; L: Leuco dye; N: Needle; P: Throughhole;
Q: Decolorizing agent; R: Reaction region; S: Side surface; la, lb, lc, Id, le:
Microchip; 11, 12, 13: Substrate layer; 2: Introduction section; 21: Introduction port;
31, 32, 33, 34, 35: Channel; 41, 42, 43, 44, 45: Well; 5: Pressure indication section; 51:
Gas-filled body; 52: Pressure indication section bottom surface; 53: Reference line; 54:
Detection material; 6: Thermal history indication section; 61: Detection material
WO 2013/118461 PCT7JP2013/000472
Claims
[Claim 1] A microchip configured to contain a sample solution for analysis, the
microchip comprising:
a channel that is maintained at a pressure level less than atmospheric
pressure so as to allow flow of the sample solution thru the channel;
and
a pressure indication section configured to detect a change in the
pressure level.
[Claim 2] The microchip according to claim 1, further comprising a substrate
layer including a self-sealing material configured to allow introduction
of the sample solution into the microchip.
[Claim 3] The microchip according to claim 2, wherein at least a portion of the
pressure indication section contacting with the self-sealing material.
[Claim 4] The microchip according to claim 3, wherein the pressure indication
section is positioned on an inner surface of the microchip.
[Claim 5] The microchip according to claim 2, further comprising a second
substrate layer including the pressure indication section and the
channel.
[Claim 6] The microchip according to claim 1, wherein the pressure indication
section includes a material that detects gas or humidity associated with
the change in pressure level.
[Claim 7] The microchip according to claim 1, wherein the pressure indication
section includes an elastic material configured to respond to the change
in the pressure level.
[Claim 8] The microchip according to claim 7, further comprising a reference
line.
[Claim 9] The microchip according to claim 1, further comprising a plurality of
pressure indication sections configured to detect the change in the
pressure level.
[Claim 10] The microchip according to claim 9, wherein a first pressure indication
section includes an elastic material configured to respond to the change
in the pressure level, and wherein a second pressure indication section
is configured to detect gas or humidity associated with the change in
pressure level.
[Claim 11] The microchip according to claim 10, wherein the first pressure in
dication section is positioned on an inner surface of the microchip and
the second pressure indication section is positioned on an outer surface
WO 2013/118461 PCT7JP2013/000472
of the microchip.
[Claim 12] The microchip according to claim 10, wherein the first pressure in
dication section is positioned on an outer surface of the microchip and
the second pressure indication section is positioned on an inner surface
of the microchip.
[Claim 13] The microchip according to claim 1, wherein the pressure indication
section is positioned on at least one of an inner surface and an outer
surface of the microchip.
[Claim 14] The microchip according to claim 1, further comprising a thermal
history indication section configured to detect a temperature change a s
sociated with the microchip.
[Claim 15] The microchip according to claim 14, wherein the thermal history in
dication section is positioned on an inner surface of the microchip.
[Claim 16] The microchip according to claim 15, wherein the pressure indication
section is positioned on an inner surface of the microchip.
[Claim 17] The microchip according to claim 14, wherein the thermal history in
dication section is positioned on an outer surface of the microchip.
[Claim 18] The microchip according to 1, further comprising a well in commu
nication with the channel, wherein the well is configured to serve as an
analysis site.
[Claim 19] The microchip according to claim 18, further comprising a plurality of
channels in communication with one or more wells.
[Claim 20] A microchip apparatus comprising a microchip configured to contain a
sample solution for analysis, wherein the microchip includes a channel
that is maintained at a pressure level less than atmospheric pressure so
as to allow flow of the sample solution thru the channel; and a pressure
indication section configured to detect a change in the pressure level.
[Claim 21] A method of manufacturing a microchip configured to contain a sample
solution for analysis, the method comprising providing the microchip
including a channel maintained at a pressure level less than at
mospheric pressure so as to allow flow of the sample solution thru the
channel, and the microchip including a pressure indication section
configured to detect a change in the pressure level.