U.S. patent application number 11/234455 was filed with the patent office on 2006-01-26 for device and method for analyizing a sample.
This patent application is currently assigned to ARKRAY, Inc.. Invention is credited to Yoshihiko Higuchi, Kouji Hirayama, Masufumi Koike, Michio Naka, Hisashi Okuda.
Application Number | 20060018790 11/234455 |
Document ID | / |
Family ID | 35694795 |
Filed Date | 2006-01-26 |
United States Patent
Application |
20060018790 |
Kind Code |
A1 |
Naka; Michio ; et
al. |
January 26, 2006 |
Device and method for analyizing a sample
Abstract
This invention provides a device for analyzing a sample which is
capable of performing rapid and precise analysis of a small amount
of sample, and whose gradient in a measuring apparatus is not
limited. This device comprises approximately a rectangular plate
shaped body comprising a base member made of resin and a
transparent covering. A first depressed cylindrical concave portion
is formed in the upper surface of the base member, and a groove is
formed in communication with the first depressed cylindrical
concave portion, the groove extending to the end of the protrusion
portion 5c, and a second depressed cylindrical concave portion
which is smaller than the first depressed cylindrical concave
portion is formed in a certain position in the groove, the end of
the groove opening to the outside at the end of the protrusion
portion 5c. Then, the transparent covering is placed over the upper
surface of the base member and then integrated together. As a
result, the first depressed cylindrical concave portion, the
groove, the second depressed cylindrical concave portion, and the
opening at the end of the groove are formed into a suction pressure
generating chamber, a drawing channel, an analytical section, and
an opening for drawing a sample, respectively.
Inventors: |
Naka; Michio; (Joyo-shi,
JP) ; Hirayama; Kouji; (Kyoto-shi, JP) ;
Higuchi; Yoshihiko; (Shijonawate-shi, JP) ; Koike;
Masufumi; (Matsubara-shi, JP) ; Okuda; Hisashi;
(Uji-shi, JP) |
Correspondence
Address: |
HAMRE, SCHUMANN, MUELLER & LARSON, P.C.
P.O. BOX 2902-0902
MINNEAPOLIS
MN
55402
US
|
Assignee: |
ARKRAY, Inc.
Kyoto-shi
JP
|
Family ID: |
35694795 |
Appl. No.: |
11/234455 |
Filed: |
September 23, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09655074 |
Sep 5, 2000 |
|
|
|
11234455 |
Sep 23, 2005 |
|
|
|
09255253 |
Feb 22, 1999 |
6180062 |
|
|
09655074 |
Sep 5, 2000 |
|
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|
08847745 |
Apr 22, 1997 |
6001307 |
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09255253 |
Feb 22, 1999 |
|
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Current U.S.
Class: |
422/400 |
Current CPC
Class: |
G01N 2021/0346 20130101;
G01N 21/03 20130101; G01N 2021/0325 20130101; B01L 2400/084
20130101; B01L 2300/0645 20130101; G01N 21/05 20130101; G01N 21/78
20130101; G01N 1/14 20130101; G01N 21/11 20130101; B01L 2200/0605
20130101; G01N 33/521 20130101; B01L 2400/0481 20130101; G01N 33/52
20130101; B01L 2300/0864 20130101; B01L 3/502746 20130101; B01L
2300/087 20130101; B01L 2300/0825 20130101; G01N 2021/0321
20130101; B01L 2300/0816 20130101; B01L 3/50273 20130101 |
Class at
Publication: |
422/058 |
International
Class: |
G01N 21/00 20060101
G01N021/00 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 26, 1996 |
JP |
8-107310 |
Sep 26, 1996 |
JP |
8-236131 |
Claims
1-27. (canceled)
28. A device for collecting a sample for analysis, comprising: a
main body dimensioned to manipulated by hand; a suction pressure
generator comprising a chamber formed in the main body; a drawing
channel formed in the main body in communication with the chamber
of the suction pressure generator, an opening in the main body
being formed at the end of said drawing channel distal with respect
to said suction pressure generator, a flexible cover on the main
body, whereby changes in pressure in the chamber of the suction
pressure generator are created by movement of the flexible cover,
and an analytical section formed in said drawing channel between
the suction generator and the opening, the analytical section
communicating directly with the exterior of the device through the
drawing channel, wherein in use a sample is drawn into the main
body through the opening by suction pressure developed by said
suction pressure generator, and then the sample is transferred by
the suction pressure through the drawing channel into the
analytical section.
29. A device as claimed in claim 28 wherein the device has at least
one dimension selected from: an overall length of 15 to 100 mm; a
width of 20 to 50 mm; a width of 5 to 20 mm; or a thickness of 1 to
5 mm.
30. A device as claimed in claim 28, wherein the device is designed
to be discarded after a single use.
31. A device as claimed in claim 30, wherein a liquid flow
resistance in a first portion of the drawing channel between said
analytical section and said suction pressure generator is greater
than a liquid flow resistance in the bypass channel and a liquid
flow resistance in a second portion of the drawing channel between
said analytical section and a position at which said bypass channel
branches.
32. A device as claimed in claim 28, wherein a positive pressure
can be generated to return a sample withdrawn from the analytical
section to the analytical section.
33. A device as claimed in claim 28, wherein the opening has a
shape enlarging toward the end.
34. A device as claimed in claim 28, wherein a liquid pooling
portion is formed between the opening and the drawing channel, and
an air vent passage branches from a portion of the drawing channel
between the liquid pooling portion and the analytical section, the
end of the air vent passage opening to the outside.
35. A device as claimed in claim 34, wherein the liquid flow
resistance in the air vent passage is larger than the liquid flow
resistance in the liquid pooling portion.
36. A device as claimed in claim 28, wherein the analytical section
formed in the drawing channel serves as a reagent positioning
section and a reagent reaction section.
37. A device as claimed in claim 28, wherein a reagent positioning
section, a reagent reaction section and an analytical section are
provided independently in certain positions in the drawing
channel.
38. A device as claimed in claim 37, wherein a plurality of reagent
positioning section are provided in certain positions in the
drawing channel.
39. A device as claimed in claim 28, wherein a concave portion with
a cylindrical inner shape is formed in the main body as the chamber
of the suction pressure generator and the flexible cover is
disposed over the concave portion.
40. A device as claimed in claim 28, wherein the analytical section
is wider than the drawing channel and the drawing channel extends
from the analytical section to the suction pressure generator.
Description
[0001] This application is a continuation of pending application
Ser. No. 09/655,074, filed Sep. 5, 2000, which is a continuation of
application Ser. No. 09/255,253, filed Feb. 22, 1999 which is a
continuation of application Ser. No. 08/847,745, filed Apr. 22,
1997, which application are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates to devices for analyzing samples such
as body fluids, to methods for analyzing samples by using such
devices, and to apparatuses for analyzing samples using such
devices.
BACKGROUND OF THE INVENTION
[0003] There are various types of samples in the field of
analytical chemistry, and particularly in the medical field, body
fluids such as blood, urine, spinal fluid, saliva and the like, are
important objects for analysis. There are needs for analyzing such
samples in large amount and collectively.
[0004] In order to meet such needs, a device for analyzing a sample
having a reagent film previously impregnated with a reagent, which
is stuck on a strip, had been developed and practically used. In
such a device, the reagent film is supplied with a sample such as
blood, where a component in the sample is reacted with the reagent
to generate a pigment, whereby a color is developed in the reagent
film, and the color is analyzed by using such a device, operations
for preparing a reagent and reacting the reagent with a component
in the sample can be simplified, thereby the whole process for
analyzing a sample becomes a routine exercise.
[0005] In such a device, examples of methods for supplying the
reagent film with a sample include, methods utilizing capillarity,
spotting, dipping, and the like. Among these methods, methods
utilizing capillarity have been most commonly used. Because it is
required to intercept external light during optical measuring, it
is necessary that a sample supplying portion and an analytical
section should be positioned away from each other when the device
is set in an optical measuring apparatus. Accordingly, a sample is
required to be transferred in the device, therefore capillarity is
utilized as a means for transferring the sample. Examples of
devices utilizing capillarity are those disclosed in Japanese
Patent Application Laid-open No. Hei 4-188065 or in Japanese Patent
Application Laid-open No. Sho 57-132900.
[0006] FIG. 22 shows a device for analyzing a sample utilizing
capillarity. As shown in the drawing, the device comprises a
triangular shaped sampling point 42 protruding from an
approximately center portion of the front face 44 of a transparent
base member 47 made of acrylic resin, a groove 46 extending from
the sampling point 42 toward the back portion of the base member
47, and a slot 45 formed as an extension of the groove.
Furthermore, a reagent film 48 is stuck on the upper face of the
base member 47 on the side of the front face 44, so that it may
cover over the groove 46. The structure of the reagent film 48 is
determined as appropriate depending upon the type of a sample. For
example, when analyzing plasma components of blood, a reagent film
having a laminated structure comprising a filtration layer, a
reagent layer, a transparent protective layer, and an opaque
protective layer, which are laminated in this order from the
bottom, in which an observation window 50 is formed for entering
light in an approximately center portion of the opaque protective
layer, is used.
[0007] A sample may be analyzed by using such a device as in the
following steps. First, a drop of blood is obtained from a subject
and brought into contact with the sampling point 42. Then, the
blood is introduced into the groove 46 by capillarity and the whole
groove is filled with the blood. When the blood permeates into the
reagent film 48 covering over the upper portion of the groove 46,
erythrocytes are first removed by the filtration layer, and plasma
components reach the reagent layer, where a pigment is generated
through a reaction between a reagent in the reagent layer and a
component in the plasma, whereby a color is developed in the
reagent layer. In this state, the device is set in an optical
measuring apparatus such as a densitometer, where the color
developed in the reagent layer may be measured by irradiating light
from the observation window 50.
[0008] However, there are problems as described below in using a
device utilizing capillarity.
[0009] First, because a capillary channel is required to be
continuously filled with a sample in order to cause capillarity, an
amount of a sample more than required for analysis is needed. In
addition, it takes some time to introduce a sample by capillarity,
so that measuring cannot be performed quickly. Furthermore, in body
fluids such as blood, there are differences among individuals in
properties such as viscosity, which affect capillarity, therefore
the time period required for introducing a sample into the
analytical part or the like cannot be fixed. As a result, it is
difficult to fix a time period required for analysis, such as time
for reaction with a reagent. Accordingly, there is a possibility
that an error might be caused in analysis results. Furthermore,
since the drawing force by capillarity is very weak, it is easily
affected by gravitational force. Therefore, when introducing a
sample, the gradient of the device should be restricted, and the
structure of an optical measuring apparatus should also be limited.
Furthermore, the sample supplying portion and the analytical
section cannot be positioned apart from each other because of the
weakness of the drawing force of capillarity, so that possibilities
of contamination during an introduction of a sample or influence of
external light cannot be completely eliminated in an optical
measuring apparatus.
[0010] On the other hand, the spotting method has a disadvantage in
that when using blood as the sample, the sampling spot is limited
to a fingertip, and sampling from an ear or the abdomen is
difficult.
SUMMARY OF THE INVENTION
[0011] The present invention has been developed in view of the
above mentioned background, and an object of the invention is to
provide a device capable of performing a rapid and precise analysis
of a small amount of a sample, a method for analyzing a sample
using such a device, and an apparatus for analyzing a sample using
such a device.
[0012] In order to solve the above-mentioned problems, the present
invention provides a device for analyzing a sample comprising a
suction pressure generating means, a drawing channel in
communication with the suction pressure generating means, an
analytical section formed in a certain position in the drawing
channel, and an opening formed at the end of the drawing channel,
wherein a sample is introduced from the opening and then drawn into
the analytical section through the drawing channel by the suction
pressure developed by the suction pressure generating means.
[0013] Accordingly, in the device of the present invention, a
sample is drawn forcefully by utilizing suction pressure in place
of capillarity as used in a conventional device. That is, a suction
pressure is developed by the suction pressure generating means, a
sample is introduced into the opening by the suction pressure, then
the sample is drawn by the suction pressure through the drawing
channels into the analytical section, where the sample is analyzed
by an optical means, an electrochemical means, or the like. Thus,
by using a suction pressure to draw a sample forcefully, it is
ensured that a small amount of a sample is introduced into the
analytical section. In addition, the time period required for
introducing the sample can be fixed to a certain short time,
irrespective of the properties of the sample such as viscosity.
Accordingly, for example, when analyzing a sample by using a
reagent, the time period for reaction between a component in a
sample and a reagent can be fixed. In addition, by drawing a sample
forcefully, for example, the amount of a sample which is reacted
with a reagent can be constantly fixed. Accordingly, errors which
might be caused in analysis results can be prevented.
[0014] Furthermore, since a sample is drawn forcefully in the
device of the present invention, it is not necessary to limit the
distance between the sample supplying portion and the analytical
section. Therefore, in the device of the present invention, the
distance between the sample supplying portion and the analytical
section can be longer than in a device utilizing capillarity.
Accordingly, influence of external light can be eliminated in an
optical measuring apparatus. Therefore, by using the device of the
present invention, a small amount of a sample can be analyzed
rapidly and precisely. Furthermore, because the sample is drawn
forcefully, the influence of gravitational force can be nearly
ignored.
[0015] In the present invention, by "suction pressure" is
understood a pressure for drawing a sample, which is usually a
negative pressure.
[0016] A sample used in the present invention is not particularly
limited as long as it can be sucked, and liquids, sols, or the like
are included in the examples. Furthermore, examples of a sample
which may be analyzed in the present invention include, whole
blood, urine, spinal fluid, blood plasma, serum, saliva, or the
like.
[0017] Method for analyzing a sample using the device of the
present invention are not particularly restricted. For example, an
optical means, an electrochemical means or the like can be applied
in such methods.
[0018] When optical measuring means is applied, either a reagent
which reacts with a component in a sample to generate a pigment, or
a reagent which reacts with a component in a sample to represent a
color in itself is generally used. However, there are some cases in
which an analysis may be conducted by using only light
transmissivity or light reflectance and without using a reagent.
One example of such a case is when analyzing a hematocrit value of
blood. Furthermore, instead of measuring transmitted light, other
optical means such as measuring reflected light, fluorescence or
the like may also be applied.
[0019] When electrochemical means is applied, a change in electric
current or in electric potential caused by the oxidation-reduction
reaction of the sample may be usually measured, and a reagent which
causes an oxidation-reduction reaction when reacted with a
component in a sample is normally used in such a measurement.
[0020] The reagent used in the present invention may be either a
dry-type or wet-type reagent. Furthermore, in a device for
simultaneous analysis of multiple items (hereinafter referred to as
"multiple analysis") as described later, various types of reagents
may be usually used depending upon the number of items to be
analyzed.
[0021] It is preferable that the device of the present invention
comprises a plurality of drawing channels, in each of which an
analytical section is formed in a certain position, the ends of the
drawing channels merging and forming one opening. By using a device
having such a structure, simultaneous analysis of multiple items,
namely multiple analysis, can be achieved. Such a device is
referred to as a device for multiple analysis.
[0022] Although suction pressure is utilized for drawing a sample
forcefully in the present invention, a suction pressure may also be
used in combination with capillarity as described later.
[0023] A device for analyzing a sample provided with a bypass
channel, and a device for analyzing a sample in which a stopper
which is gas-permeable and liquid-impermeable is formed, are
preferred embodiments of the present invention. As described above,
the device of the present invention has many advantages by
utilizing suction pressure for drawing a sample forcefully.
However, because such a forced sucking is markedly strong compared
to a sucking utilizing capillarity, there is a possibility that a
sample might pass through the analytical section and does not
remain there. The above embodiments of the present invention
provide a solution for such a problem. When using either of the
above-described embodiments of the present invention, it is not
necessary to be particularly careful when generating a suction
pressure, therefore allowing simpler manipulation.
[0024] Accordingly, in a first preferred embodiment, a device for
analyzing a sample of the present invention includes a suction
pressure generating means, a drawing channel in communication with
the suction pressure generating means, an analytical section formed
in a certain position in the drawing channel, the end of the
drawing channel forming an opening, and in addition provided with a
bypass channel which branches from a portion of the drawing channel
between the analytical section and the opening and is in
communication with the suction pressure generating means, wherein
the relationship of the liquid flow resistance (X) in the drawing
channel between the analytical section and the suction pressure
generating means, the liquid flow resistance (Y) in the bypass
channel, and the liquid flow resistance (Z) in the drawing channel
between the branching portion of the bypass channel and the
analytical section is such that X>Y>Z.
[0025] In this embodiment, when the developed suction pressure is
large, an excess of suction pressure may still remain even after a
sufficient amount of a sample has been introduced into the
analytical section or the like. In case that an excess of suction
pressure remains, there are possibilities that a sample which has
been introduced into the analytical section or the like might
further be drawn into the suction pressure generating means, that
air might be entrained in the analytical section, or that a pigment
generated through reaction between a component in the sample and a
reagent might flow into the suction pressure generating means. This
first preferred embodiment solves such problems by providing a
bypass channel, and also by having the relationship of the liquid
flow resistance (Y) in the bypass channel and the liquid flow
resistances (X, Z) in the two portions of the drawing channel is
such that X>Y>Z.
[0026] Accordingly, because the liquid flow resistance (Z) in the
drawing channel between the branching portion of the bypass channel
and the analytical section is the smallest among the three liquid
flow resistances (X), (Y), and (Z), even if a suction pressure
larger than required is generated by the suction pressure
generating means, a sample is first introduced from the opening and
drawn into the analytical section in a sufficient amount. In this
case, even if an excess amount of a sample and/or entrained air are
drawn by the excess suction pressure, the excess of a sample and/or
the entrained air can be introduced into the bypass channel, while
the sample introduced into the analytical section, a generated
pigment and the like remain in the analytical section. This is
because the liquid flow resistance (X) in the drawing channel
between the analytical section and the suction pressure generating
means is larger than the liquid flow resistance (Y) in the bypass
channel. Then, the excess of a sample and the entrained air may be
discharged into the bypass channel or through the bypass channel
into the suction pressure generating means. Accordingly, even if a
large suction pressure is generated, it is ensured that a sample is
introduced into the analytical section to be analyzed, therefore
further rapid and precise analysis of the sample can be
achieved.
[0027] In the present invention, by "liquid flow resistance" is
understood a resistance to flow to which liquid is subjected when
moving through a channel, and serves as a criterion for ease of
liquid flow.
[0028] Suitable methods for controlling the liquid flow resistance
in each of the channels are, for example, changing the diameter of
the channel, treating the inner surface of the channel which
contacts with liquid by using a detergent, a water repellent agent
or the like in order to change the wettability. Examples of the
water repellent agents are silicon, tetrafluoroethylene resin, and
the like.
[0029] In order to perform multiple analysis as described above, it
is preferable that the first preferred embodiment of the present
invention is provided with a plurality of drawing channels, an
analytical section formed in a certain position in each of the
drawing channels, the ends of the respective drawing channels
merging and forming one opening, and a bypass channel branching
from a portion of the drawing channel between the merging portion
and the opening and being communicated with the suction pressure
generating means.
[0030] A second preferred embodiment comprises a suction pressure
generating means, a drawing channel in communication with the
suction pressure generating means, an analytical section formed in
a certain position in the drawing channel, an opening being formed
at the end of the drawing channel, and further comprising a stopper
which is gas-permeable and liquid-impermeable (hereinafter referred
to as a "stopper") formed in a certain position in the drawing
channel between the suction pressure generating means and the
analytical section, by which a flow of a sample into the suction
pressure generating means can be prevented.
[0031] In the second embodiments, the portion of the drawing
channel between the analytical section and the suction pressure
generating means where the stopper may be formed should include
both the boundary portion between the drawing channel and the
suction pressure generating means, and the boundary portion between
the drawing channel and the analytical section.
[0032] In the second embodiment, the stopper is usually made of a
hydrophobic porous material.
[0033] It is preferable that the second embodiment be made for
multiple analysis as described below.
[0034] That is, in the second embodiment, it is preferable that a
plurality of analytical sections are formed in certain position in
the drawing channel, and that a stopper is formed in a portion of
the drawing channel between the suction pressure generating means
and the analytical section which is the closest to the suction
pressure generating means.
[0035] Furthermore, it is preferable that the second embodiment be
provided with a plurality of drawing channels, and an analytical
section formed in a certain position in each of the drawing
channels, the ends of the respective drawing channels merging and
forming one opening.
[0036] It is preferable that the opening of the drawing channel is
enlarged toward the end, that is, funnel-shaped. By having such a
shape, a sample such as blood can be retained in the opening after
the sample is introduced, therefore subsequent drawing operation
becomes easier. In addition, air inclusion can also be reduced.
Especially in case of sampling blood from a small spot such as a
fingertip, it is required to ensure that the opening for the
drawing channel in the device is contacted with the sampling spot
until introduction of the sample is completed. Therefore,
substantial attention is required for controlling sampling,
resulting in more complex operation. Furthermore, since an amount
of blood which can be obtained from a fingertip or the like is as
little as several 10 .mu.l, air inclusion may easily occur in a
conventional device for analyzing a sample during introduction of a
sample, thereby greatly affecting the measured results. In order to
solve such problems, the opening for the drawing channel is formed
into a funnel-shape, so that the sample can be retained there. By
having such a structure, it is possible to draw the sample through
the channel after detaching the opening from the sampling spot,
therefore a sample can be easily obtained from a small spot without
causing air inclusion.
[0037] Furthermore, it is also preferable that the device be
provided with a liquid pooling portion formed between the opening
and the drawing channel, and an air vent passage branching from a
portion of the drawing channel between the liquid pooling portion
and the analytical section, the end of the air vent passage opening
to the outside of the device. The air vent passage branches from a
portion of the drawing channel between the liquid pooling portion
and the analytical section so that air inclusion can be prevented
during introduction of the sample.
[0038] By providing such a liquid pooling portion and an air vent
passage, a sample can be introduced by capillarity developed by the
air vent passage and retained in the liquid pooling portion,
therefore subsequent sucking operation can be performed without
causing air inclusion after detaching the opening from the sampling
spot.
[0039] It is preferable that the liquid flow resistance in the air
vent passage is larger than that in the liquid pooling portion, so
that air inclusion can be further prevented.
[0040] Suitable methods for controlling the liquid flow resistance
are, for example, changing the dimension of a cross section,
treating the surface which contacts with liquid by using a surface
active agent, a water repellent agent or the like to change the
wettability. Examples of the water repellent agent include silicon,
tetrafluoroethylene resin, and the like. It is preferable that the
liquid flow resistance should be controlled by changing dimensions
of a cross section in view of controllability. For example, the
thickness and the width of the liquid pooling portion may be formed
larger than those of the air vent passage.
[0041] In the device of the present invention, the analytical
section formed in the drawing channel may serve both as a reagent
positioning section and a reagent reaction section. Alternatively,
a reagent positioning section, a reagent reaction section, and an
analytical section may be provided independently in certain
positions in the drawing channel. Still alternatively, a plurality
of reagent reaction sections, reagent positioning sections, and
analytical sections may be provided in certain positions in the
drawing channel.
[0042] In the device of the present invention, an analytical
section preferably serves both as a reagent positioning section and
as a reagent reaction section. However, if a reagent can move
through the drawing channel, a reagent positioning section, a
reagent reaction section, and an analytical section (hereinafter
also referred to as a "measuring section") may be independently
formed in certain positions in the drawing channel. In such a
device, a sample and a reagent can be mixed and stirred while the
sample moves between each of the respective sections, and also in
case of using a dry-type reagent, dissolution of the reagent may be
facilitated. The reagent may move either independently or together
with the sample.
[0043] Furthermore, such a device can be applied for multiple steps
reaction including a pre-treatment step. For example, if a
plurality of reagent reaction sections or the like are provided in
series in the drawing channel, a sample can be transferred to the
respective sections, while causing reactions respectively. By using
such a device, for example, in case of performing analysis
utilizing antigen-antibody reaction, in which B/F separation is
required, B/F separation can be performed by transferring a sample
and a rinsing solution among the respective reagent reaction
sections or the like.
[0044] Furthermore, in case of using a reagent consisting of two or
more components, which cannot be mixed prior to reaction with a
sample, it is preferred that a plurality of reagent positioning
sections are provided in certain positions in the drawing
channel.
[0045] Next, in the device for analyzing a sample of the present
invention, a suction pressure generating chamber, a suction
pressure generating tube or the like capable of changing the
volume, may be used as a suction pressure generating means. A vent
may be formed in the suction pressure generating chamber. With
regard to the suction pressure generating tube, a suction pressure
is generated by drawing the tube through a hand.
[0046] In the device of the present invention, when analyzing a
sample by using an electrochemical means, it is preferable that the
analytical section is provided with a pair of electrodes comprising
a working electrode and a counter electrode.
[0047] According to another aspect of the present invention, a
method for analyzing a sample comprises preparing the device of the
present invention, generating a suction pressure by the suction
pressure generating means, thereby introducing a sample into the
opening, and drawing the sample by the suction pressure through the
drawing channel into the analytical section, where analysis of the
sample is performed.
[0048] A method for analyzing a sample using the first or the
second embodiment of the present invention will be described.
[0049] A method for analyzing a sample using the first embodiment
of the device of the present invention comprises the steps of
preparing the first embodiment, developing a suction pressure by
the suction pressure generating means, thereby introducing a sample
into the opening, and drawing the sample by the suction pressure
through the drawing channel into the analytical section, while
excess amount of the sample and/or entrained air are discharged
into the bypass channel and also through the bypass channel into
the suction pressure generating means, thereupon performing an
analysis of the sample.
[0050] A method for analyzing a sample using the second embodiment
comprises the steps of preparing the second embodiment, developing
a suction pressure by the suction pressure generating means,
thereby introducing a sample into the opening, drawing the sample
by the suction pressure through the drawing channel into the
analytical section, where analysis of the sample is performed.
[0051] When multiple analysis is conducted in these methods,
multiple items may be simultaneously analyzed by using a device for
multiple analysis.
[0052] These methods for analyzing a sample, in which either a
device having a funnel-shaped opening or a device provided with a
liquid pooling portion and an air vent passage is used, comprise
the steps of preparing the device for analyzing a sample,
contacting the opening with a sample, thereby drawing the sample
into the opening or into the liquid pooling portion by capillarity
to retain the sample, and then generating a suction pressure by the
suction pressure generating means, drawing the sample retained in
the opening or in the liquid pooling portion by the suction
pressure through the drawing channel into the analytical section,
where analysis of the sample is performed.
[0053] According to the method for analyzing a sample using either
a device provided with a funnel-shaped opening or a device in which
a liquid pooling portion and an air vent passage are formed, for
example, the device can be detached from a sampling spot after
contacting the opening with a sample in the sampling spot to
introduce the sample into the opening or into the liquid pooling
portion, where the sample is retained, therefore making the
subsequent sucking operation easier.
[0054] In these methods for analyzing a sample of the present
invention, the means of analysis is not particularly limited, and
for example, an optical means or an electrochemical means is
used.
[0055] Furthermore, apparatus for analyzing a sample of the present
invention may be either an optical measuring apparatus or an
electric measuring apparatus.
[0056] The optical measuring apparatus comprises an optical
measuring system provided with a light irradiating section and a
light detecting section, and a device for a analyzing a sample,
wherein the device is positioned so that the analytical section of
the device can be irradiated with light from the light irradiating
section, and so that the detecting section can detect transmitted
light, fluorescence, or reflected light in the analytical
section.
[0057] The electric measuring apparatus comprises an electric
signal generating means, an electric signal detecting means, and a
device for analyzing a sample, wherein the working electrode of the
device and the electric signal generating means are connected to
each other, and the counter electrode of the device and the
electric signal detecting means are connected to each other.
BRIEF DESCRIPTION OF THE DRAWINGS
[0058] The above and other objects, features and advantages of the
present invention will be apparent from the following detailed
description of the preferred embodiments of the invention in
conjunction with the accompanying drawings, in which:
[0059] FIG. 1(A) is a plan view of one embodiment of the device for
analyzing a sample of the present invention, and FIG. 1(B) is a
cross-sectional view of the device of the FIG. 1(A) taken along the
line I-I.
[0060] FIG. 2 is a plan view of another embodiment of the device of
the present invention.
[0061] FIG. 3 is a plan view of still another embodiment of the
device of the present invention.
[0062] FIG. 4 is a plan view of still another embodiment of the
device of the present invention.
[0063] FIG. 5(A)-5(D) are plan views showing a stepwise process for
drawing a sample in one embodiment of the device of the present
invention in which a bypass channel is provided.
[0064] FIG. 6(A) is a plan view of still another embodiment of the
device of the present invention, and FIG. 6(B) is a cross-sectional
view of the device of the FIG. 6(A) taken along the line II-II.
[0065] FIG. 7 is a plan view of still another embodiment of the
device of the present invention.
[0066] FIG. 8 is a plan view of still another embodiment of the
device of the present invention.
[0067] FIG. 9(A) is a plan view of still another embodiment of the
device of the present invention, and FIG. 9(B) is a cross-sectional
view of the device of the FIG. 9(A) taken along the line II-II.
[0068] FIG. 10 is a perspective view showing the fabrication of the
device shown in FIG. 9.
[0069] FIG. 11(A) is a plan view of the device shown in FIG. 9, in
which a sample is introduced and retained in the liquid pooling
portion, and FIG. 11(B) is a plan view of the device shown in FIG.
9, in which a sample is drawn into the analytical section.
[0070] FIG. 12 is a plan view of still another embodiment of the
device of the present invention.
[0071] FIG. 13 is a plan view of still another embodiment of the
device of the present invention.
[0072] FIG. 14 is a plan view of still another embodiment of the
device of the present invention.
[0073] FIG. 15 is a plan view of still another embodiment of the
device of the present invention.
[0074] FIG. 16 is a plan view of still another embodiment of the
device of the present invention.
[0075] FIG. 17(A)-(D) are cross-sectional views showing a process
for drawing a sample in a still another embodiment of the device of
the present invention.
[0076] FIG. 18(A)-(D) are cross-sectional views showing a process
for drawing a sample in a still another embodiment of the device of
the present invention.
[0077] FIG. 19(A) is a plan view showing a still another embodiment
of the device of the present invention, and FIG. 19(B) is a
cross-sectional view of the device of the FIG. 19(A) taken along
the line IV-IV.
[0078] FIG. 20 is a perspective view showing the fabrication of the
device shown in FIG. 19.
[0079] FIG. 21(A)-(H) are plan views showing an analysis using a
still another embodiment of the device of the present
invention.
[0080] FIG. 22 is a perspective view of a conventional device for
analyzing a sample.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
[0081] Next, embodiments of the present invention will be
described. In the following embodiments, unless particularly shown
otherwise, the analytical section serves both as a reagent
positioning section and a reagent reaction section.
EXAMPLE 1
[0082] FIG. 1 shows an embodiment of a device for analyzing a
sample of the present invention. FIG. 1(A) is a plan view showing
such a device, and FIG. 1(B) is a cross-sectional view showing the
device of FIG. 1(A) taken along the line I-I.
[0083] As shown in the drawings, one end portion of the rectangular
plate shaped body 5 (i.e. the left end portion in the drawings) is
formed into a protrusion portion 5c which has a smaller width than
that of the body. The width of the protrusion portion 5c is
decreasing toward the end. Furthermore, the body 5 comprises a base
member 5b and a covering 5a which covers over the base member. The
base member 5b and the covering 5a are usually integrated together
by using an adhesive such as a hot melt adhesive.
[0084] In the upper surface side of the base member 5b, a first
depressed cylindrical concave portion, which forms a suction
pressure generating chamber, is formed in a portion on one end side
(right side in the drawings) relative to the center portion, a
groove which forms a drawing channel 2 is formed in communication
with the first depressed cylindrical concave portion, the groove
extending to the end of the protrusion portion 5c, a second
depressed cylindrical concave portion which is smaller than the
first depressed cylindrical concave portion, which will form an
analytical section 3, is formed in a certain position in the groove
at an approximately center portion of the body 5, and further the
end of the groove opens to the outside at the end of the protrusion
portion 5c, thereby forming an opening 4 for drawing a sample.
Then, by covering the surface of the base member 5b with a covering
5a and integrating both of them together, the first depressed
cylindrical concave portion, the groove, the second depressed
cylindrical concave portion, and the end of the groove become the
suction pressure generating chamber 1, the drawing channel 2, the
analytical section 3, and the opening 4, respectively.
[0085] Furthermore, in subsequent embodiments, a suction pressure
generating chamber, a drawing channel, a bypass channel, and the
like are formed by forming depressed cylindrical concave portions
and a groove as in this embodiment.
[0086] Although a reagent is not shown in the drawings, when the
covering 5a is transparent and light may be irradiated through the
covering (from the side of the covering), for example, a reagent
film impregnated with a reagent may be stuck on the inner surface
of the covering 5a corresponding to the analytical section 3.
Furthermore, in the drawings, 2a refers to the portion of the
drawing channel 2 between the opening 4 and the analytical section
3, and 2b refers to the portion of the drawing channel 2 between
the analytical section 3 and the suction pressure generating
chamber 1, respectively.
[0087] The dimensions of the device are usually 20 to 50 mm in
overall length, 10 to 30 mm in width, 1 to 5 mm in overall
thickness, 10 to 20 mm in length of the protrusion portion, 5 to 10
mm in maximum width of the protrusion portion, and 3 to 5 mm in
minimum width of the protrusion portion. Furthermore, the
dimensions of the suction pressure generating chamber 1 are usually
10 to 20 mm in diameter, 0.2 to 1 mm in depth, and the dimensions
of the analytical section 3 are usually 2 to 5 mm in diameter and
0.1 to 0.5 mm in depth. Furthermore, the dimensions of the drawing
channel 2 are usually 15 to 40 mm in overall length, 1 to 3 mm in
width, and 0.1 to 0.5 mm in depth, in which the drawing channel 2b
between the suction pressure generating chamber 1 and the
analytical section 3 is 5 to 20 mm in length, and the drawing
channel 2a between the analytical section 3 and the opening 4 is 10
to 30 mm in length.
[0088] Examples of the material for the base member 5b include
acrylonitrile butadiene styrene copolymer (ABS resin), polystyrene,
Noryl resin, polyethylene, polyethylene terephthalate (PET), and
acrylic resin. It is particularly preferred to use polystyrene or
acrylic resin in view of light transmissivity and the like.
[0089] It is required that the covering 5a have an elastic
property. Moreover, when light is irradiated through the covering,
it is also required that at least the portion of the covering
corresponding to the analytical section 3 should be transparent.
Examples of suitable materials for the covering are PET,
polyethylene, and vinyl chloride. In particular, it is preferred to
use PET in view of processability and dimensions.
[0090] The reagent is usually contained in a reagent film as
previously described, and the structure of the reagent film is
determined as appropriate depending upon the type of the object for
analysis. For example, when plasma components of blood is the
object for analysis, a reagent film having a structure in which a
filtration layer for separating erythrocytes, a reagent layer
impregnated with a reagent, and a base member are laminated in this
order is usually used. Furthermore, the reagent film is arranged in
the analytical section 3 in such a manner that the filtration layer
may contact with blood (the sample), and that irradiating light may
enter from the side of the transparent protective layer. In
addition, conventionally known materials may be used for the
respective layers of the reagent film.
[0091] For example, an analysis using this device may be conducted
as follows.
[0092] First, the portion of the covering 5a corresponding to the
suction pressure generating chamber 1 of the device is compressed
by applying a pressure, for example, by pressing with a finger.
Then, in this state, the opening 4 at the end of the protrusion
portion 5c is contacted with a sample. Then, the pressure applied
to the chamber is released by weakening the pressing force with a
finger so that the compressed portion of the covering 5a can return
to its original shape due to the elasticity of the covering. At
this time, a suction pressure is generated, whereby the sample is
introduced into the opening 4, and then the sample is further drawn
through the drawing channel 2a into the analytical section 3. The
time period required for introduction of the sample into the
analytical section 3 in this device is markedly short compared to a
case of using a device utilizing capillarity. In addition, such
time is hardly affected by the properties of the sample such as
viscosity. Then, a reaction between a component in the sample and
the reagent contained in the reagent film takes place in the
analytical section 3 to generate a pigment, whereby a color is
developed in the reagent film. Then, the device in which a color is
developed in the reagent film is set in a predetermined position in
an optical measuring apparatus such as a densitometer. Then, light
is irradiated into the device through the covering 5a, whereby when
using the densitometer, a reflected light is detected in a
detecting section to measure the developed color. When both the
base member 5b and the reagent film are also transparent, the
sample can also be analyzed by using transmitted light.
EXAMPLE 2
[0093] Next, FIG. 2 is a plan view showing an embodiment of a
device for multiple analysis of the present invention. The device
for multiple analysis is capable of analyzing three items
simultaneously.
[0094] As shown in the drawing, one end portion of the rectangular
plate shaped body 5 (the left end in the drawing) is formed into a
protrusion portion 5c, which is smaller than the body in width in
this device. The width of the protrusion portion 5c is decreasing
toward the end. Furthermore, the body 5 comprises a base member and
a covering which covers over the base member in this device like in
the predescribed embodiment.
[0095] Like in the device in Example 1, in the upper surface of the
base member, three drawing channels 2b extend from a suction
pressure generating chamber 1 formed in one end side portion of the
body (right side in the drawings) relative to the center of the
body. At the end of each drawing channel 2 is formed an analytical
section 3, different types of reagents (not shown) being disposed
in the respective analytical sections 3, and three drawing channels
2a extend from the respective analytical sections 3, the ends of
the drawing channels 2a merging and forming one opening 4. When the
covering is transparent, the reagents are disposed by sticking
reagent films on the portions of the inner surface of the covering
corresponding to the respective analytical sections 3.
[0096] In such a device for multiple analysis, overall dimensions
are determined as appropriate depending upon the number of the
items to be analyzed. Because three items are analyzed in this
embodiment, the dimensions of the device are usually 30 to 80 mm in
overall length, 20 to 50 mm in width, 1 to 5 mm in overall
thickness, 10 to 20 mm in length of the protrusion portion, 5 to 10
mm in maximum width of the protrusion portion, 3 to 5 mm in minimum
width of the protrusion portion.
[0097] Other things such as the materials, dimensions of the
suction pressure generating chamber, the drawing channels and the
like, are the same as in the predescribed embodiment of a device
for analyzing a sample. Furthermore, the number of items to be
analyzed is not particularly limited; however, it is usually
between 1 and 20, preferably between 3 and 5. In such a case,
various numbers of analytical sections and drawing channels may be
formed depending upon the number of the items to be analyzed.
[0098] For example, an analysis using such a device for multiple
analysis may be performed as follows.
[0099] First, a portion of the covering 5a corresponding to the
suction pressure generating chamber 1 of the device is compressed
by applying a pressure, for example, by pressing with a finger.
Then, in this state, the opening 4 at the end of the protrusion
portion is contacted with a sample. Then, the applied pressure to
the chamber is released by weakening the pressing force with a
finger so that the compressed portion of the covering may return to
its original shape due to the elasticity of the covering. At this
time, a suction pressure is generated, whereby the sample is drawn
into the opening 4 and then further drawn through the three drawing
channels 2a to the three analytical sections 3. Like in the
embodiment in Example 1, the time period required for the
introduction of the sample into the respective analytical sections
3 in this device is markedly short compared to that in a device
using capillarity. In addition, the time is hardly affected by the
properties of the sample such as viscosity. Then, reactions between
components in the sample and the reagents contained in the
respective reagent films take place to generate pigments in the
respective analytical sections 3, whereby colors are developed in
the respective reagent films. Then, the device in which colors are
developed in the respective reagent films is set in a predetermined
position in an optical measuring apparatus such as a densitometer.
Then, light is irradiated into the device, so that when using the
densitometer, a reflected light may be detected in a detecting
section to measure the developed color, so that three items can be
analyzed simultaneously.
EXAMPLE 3
[0100] FIG. 3 shows a plan view of an embodiment of a device for
analyzing a sample of the present invention provided with a bypass
channel.
[0101] As shown in the drawing, one end side portion of the
rectangular plate shaped body 5 (the left end in the drawing) is
formed into a protrusion portion 5c, which is smaller than the body
in width. The width of the protrusion portion 5c is decreasing
toward the end. Furthermore, the body 5 comprises a base member and
a covering which covers over the base member in the device like in
the predescribed embodiment.
[0102] Like in the embodiment in Example 1, in the upper surface of
the base member 5b, a drawing channel 2b extends from a suction
pressure generating chamber 1 formed in one end side portion of the
body 5 (right side in the drawing) relative to the center of the
body. At the end of the drawing channel 2b is formed an analytical
section 3, and a reagent (not shown) is disposed in the analytical
section 3, and further a drawing channel 2a extends from the
analytical section 3 toward the end of the protrusion portion 5c.
At the end of the drawing channel 2a is formed an opening 4. Where
the covering is transparent, the reagent is disposed by sticking a
reagent film on a portion of the inner surface of the covering
corresponding to the analytical section 3. A bypass channel 6
branches from a portion of the drawing channel 2a between the
opening 4 and the analytical section 3, and extends to communicate
with the suction pressure generating chamber 1.
[0103] Furthermore, the relationship among three liquid flow
resistances, namely, the liquid flow resistance (X) in the drawing
channel 2b between the suction pressure generating chamber 1 and
the analytical section 3, the liquid flow resistance (Y) in the
bypass channel, and the liquid flow resistance (Z) in the drawing
channel 2a between the branching portion of the bypass channel 6
and the analytical section 3 is such that X>Y>Z.
[0104] As shown in the drawing, the entire drawing channel 2a has a
large diameter, so that the liquid flow resistance (Z) is the
smallest among the three, the bypass channel 6 includes a certain
length of a channel 6a having a small diameter extending from the
branching portion, so that the liquid flow resistance (Y) is the
second smallest, and the entire drawing channel 2b has a small
diameter, so that the liquid flow resistance (X) is the
largest.
[0105] The drawing channel 2a is usually 10 to 30 mm in length, 1
to 3 mm in width, 0.1 to 0.5 mm in depth. The bypass channel 6 is
usually 10 to 30 mm in overall length wherein the bypass channel 6a
having a small diameter is 0.5 to 5 mm in length, 0.1 to 0.5 mm in
width, and 0.1 to 0.5 mm in depth, and also the portion of the
bypass channel having a large diameter is 1 to 3 mm in width and
0.1 to 0.5 mm in depth. The drawing channel 2b is usually 0.5 to 30
mm in length, 0.1 to 0.5 mm in width, and 0.1 to 0.5 mm in
depth.
[0106] In such a device having the bypass channel 6, the overall
dimensions, materials, dimensions of the suction pressure
generating chamber and the like, and so forth, are the same as
those of the device in Example 1.
[0107] Next, FIG. 4 shows a plan view of an embodiment of a device
having the bypass channel 6 in which the channel 6a having a small
diameter is relatively long. In such a device, the bypass channel 6
is usually 10 to 30 mm in overall length, wherein the bypass
channel 6a having a small diameter is 3 to 10 mm in length, 0.1 to
0.5 mm in width, and 0.1 to 0.5 mm in depth, and also the portion
of the bypass channel having a large diameter is 1 to 3 mm in width
and 0.1 to 0.5 mm in depth. By having such a relatively long bypass
channel 6a having a small diameter, it is possible to provide a
large difference between the liquid flow resistance (Y) in the
bypass channel 6 and the liquid flow resistance (Z) in the drawing
channel 2a between the branching portion of the bypass channel 6
and the analytical section 3.
[0108] In the device shown in FIG. 4, the width of the opening 4 is
increasing toward the end, that is, funnel-shaped. By having such a
shape, a sample can be retained in the funnel-shaped opening 4
during sampling, therefore the subsequent sucking operation can be
performed smoothly, while air inclusion can be prevented. The
opening 4 is usually 3 to 6 mm in maximum width, 1 to 3 mm in
minimum width, and 1 to 5 mm in length.
[0109] Other than the bypass channel 6 and the opening 4, the
structure of the device shown in FIG. 4 is the same as that of the
device shown in FIG. 3.
[0110] An analysis using such a device having a bypass channel
(FIG. 3 or 4) is conducted, for example, as follows.
[0111] First, a portion of the covering corresponding to the
suction pressure generating chamber 1 of the device is compressed
by applying a pressure, for example, by pressing with a finger.
Then, in this state, the opening 4 at the end of the protrusion
portion 5c is contacted with a sample. Then, in this state, the
pressure applied to the chamber is released by weakening the force
of pressing with a finger, so that the compressed portion of the
covering can return to its original shape due to the elasticity of
the covering. At this time, a suction pressure is developed, and if
the developed suction pressure is larger than required, the sample
is drawn in a manner, such as shown in FIG. 5. That is, because the
liquid flow resistance (Z) in the drawing channel 2a between the
branching portion of the bypass channel 6 and the analytical
section 3 is the smallest among the three liquid stresses as
described above, a sample 15 is first introduced into the opening 4
and further drawn through the drawing channel 2a into the
analytical section 3 as shown in FIG. 5(A). If an excess of suction
pressure still remains, because the liquid flow resistance (Y) in
the bypass channel 6a is smaller than the liquid flow resistance
(X) in the drawing channel 2b, an excess amount of the sample 15
and/or entrained air will flow into the bypass channel 6 as shown
in FIG. 5(B), and further part of them may flow into the suction
pressure generating chamber 1 as shown in FIG. 5(C). At this time,
because the liquid flow resistance (X) in the drawing channel 2b is
the largest of the three, the sample introduced into the analytical
section 3 remains there, where a reaction between a component in
the sample and a reagent (not shown) takes place to generate a
pigment, thereby developing a color in the reagent film. In
addition, a possibility that the pigment might flow into the
suction pressure generating chamber 1 can be eliminated.
Furthermore, if an excess of suction pressure still remains, the
excess amount of the sample 15 and/or entrained air present in the
bypass channel 6 is further discharged into the suction pressure
generating chamber 1 as shown in FIG. 5(D).
[0112] Then, the device in which a color is developed in the
reagent film is set in a predetermined position in an optical
measuring apparatus such as a densitometer. Then, light is
irradiated into the device, so that when using the densitometer,
reflected light is detected in a detecting section to measure the
developed color.
[0113] Thus, by having the bypass channel in the device and also
providing said relationship of the liquid stresses in the three
portion of the channels, even if excess suction pressure is
developed, the sample is ensured to be introduced into the
analytical section, where the sample undergoes reaction with a
reagent. Moreover, a possibility of overflow of the generated
pigment can be eliminated. Accordingly, by using such a device
having a bypass channel, rapid sampling can be conducted without
carefully adjusting the force of pressing with a finger.
EXAMPLE 4
[0114] FIG. 6 shows an embodiment of a device for analyzing a
sample of the present invention in which an analytical section is
formed in the under surface side of the body. In this device, light
is irradiated from the under surface side of the body. FIG. 6(A) is
a plan view of such a device, and FIG. 6(B) is a cross-sectional
view of the device in FIG. 6(A) taken along the line II-II.
[0115] As shown in the drawings, this device comprises an
approximately rectangular plate shaped body 5, the body 5
comprising a base member 5b and a covering 5a which covers over the
surface of the base member.
[0116] In the upper surface of the base member 5b, a suction
pressure generating chamber 1 is formed in a portion on one end
side of the body 5 (left side in the drawings) relative to the
center of the body 5, from which a drawing channel 2b extends
toward the other end side of the body. Then, the drawing channel 2b
extends downwards from the upper surface side to the under surface
side of the base member, where the channel communicates with one
end side of the analytical section 3 formed in the under surface
side of the base member 5b. As shown in the drawings, a reagent
film 7 is disposed in the analytical section 3. Then, a drawing
channel 2a extends from the other end side of the analytical
section 3 to reach the upper surface side of the base member 5b,
and then further extends toward the other end side of the body (the
opposite side to the suction pressure generating chamber 1) in the
upper surface side of the base member 5b, the end of the channel
forming an opening 4. The opening 4 is formed into a funnel shape.
Furthermore, a bypass channel 6 also extends from the suction
pressure generating chamber 1, the end of the bypass channel
merging into the drawing channel 2a between the analytical section
3 and the opening 4. A portion of the bypass channel 6 from the
merging portion is formed to be a bypass channel 6a having a small
diameter, while the whole drawing channel 2b has a small diameter,
and the whole drawing channel 2a has a large diameter. As a result,
the relationship of the liquid flow resistance (X) in the drawing
channel 2b, the liquid flow resistance (Y) in the bypass channel
6a, and the liquid flow resistance (Z) in a portion of the drawing
channel 2a between the branching portion of the bypass channel 6
and the analytical section 3 is X>Y>Z.
[0117] In this device, the covering 5a is not necessarily
transparent, however, it may be transparent so that the process of
drawing a sample can be observed.
[0118] Furthermore, the materials of the base member 5b and the
covering 5a, the dimensions of the suction pressure generating
chamber, the drawing channel, and the like in the device are the
same as in the device of the embodiment previously described.
[0119] Next, an analysis using such a device is conducted, for
example, as follows.
[0120] First, a portion of the covering 5a corresponding to the
suction pressure generating chamber 1 of the device is compressed
by applying a pressure, for example, by pressing with a finger.
Then, in this state, the opening 4 is contacted with a sample.
Then, the pressure applied to the chamber is released by weakening
the force of pressing with a finger so that the compressed portion
of the covering 5a can return to its original shape due to the
elasticity of the covering. At this time, a suction pressure is
generated, whereby the sample is drawn into the opening 4, and then
further drawn through the drawing channel 2a into the analytical
section 3. By having the bypass channel 6 and providing the
relationship of the three liquid flow resistances (X,Y,Z) of
X>Y>Z in this device, even if excess suction pressure is
generated, the sample is ensured to be introduced into the
analytical section 3, where the sample undergoes reaction with a
reagent. In addition, a possibility that a generated pigment might
flow into the suction pressure generating chamber 1 can be
eliminated. Then, the device in which a color is developed in the
reagent film is set in a predetermined position in an optical
measuring apparatus such as a densitometer. Then, light L is
irradiated into the device from the under surface side of the base
member 5b, so that when using the densitometer, a reflected light
is detected in a detecting section to measure the developed
color.
EXAMPLE 5
[0121] Next, FIG. 7 shows a plan view of an embodiment of a device
for multiple analysis of the present invention. This device for
multiple analysis is capable of analyzing three items
simultaneously.
[0122] As shown in the drawing, one end portion of the rectangular
plate shaped body 5 (the left end in the drawing) in this device is
formed into a protrusion portion 5c, which is smaller than the body
in width. The width of the protrusion portion 5c is decreasing
toward the end. Furthermore, the body 5 comprises a base member and
a covering which covers over the surface of the base member as in
the predescribed embodiment.
[0123] In the upper surface of the base member, three drawing
channels 2b extend from a suction pressure generating chamber 1
formed in one end side portion of the body (right side in the
drawing) relative to the center of the body. At each end of the
respective drawing channels 2b is formed an analytical section 3,
different types of reagents (not shown) being disposed in the
respective analytical sections 3, and three drawing channels 2a
extend from the respective analytical sections 3, the ends of the
respective drawing channels 2a merging into one opening 4. When the
covering is transparent, the reagents are disposed by sticking
reagent films on the inner surface of the covering corresponding to
the respective analytical sections 3. A bypass channel 6 extends
from the suction pressure generating chamber 1, the end of the
bypass channel merging into the opening 4. A certain portion of the
bypass channel 6 from the merging portion is formed as a bypass
channel 6a having a small diameter, while the whole drawing
channels 2b have small diameters, and the whole drawing channels 2a
have large diameters. As a result, the relationship of the liquid
flow resistance (X) in the drawing channels 2b, the liquid flow
resistance (Y) in the bypass channel 6, and the liquid flow
resistance (Z) in the portions of the drawing channels 2a between
the branching portion of the bypass channel 6 and the analytical
sections 3 is X>Y>Z.
[0124] In such a device for multiple analysis, the overall
dimensions are determined as appropriate depending upon the number
of the items to be analyzed. Because three items are to be analyzed
in this embodiment, the dimensions of the device are usually 20 to
50 mm in overall length, 20 to 50 mm in width, and 1 to 5 mm in
overall thickness, wherein the protrusion portion is 10 to 20 mm in
length, 5 to 20 mm in maximum width, 3 to 5 mm in minimum width.
Other things such as materials, dimensions of the suction pressure
generating chamber, the drawing channels and the like, and so forth
in this device are the same as in the device of prescribed
embodiment having a bypass channel. Furthermore, the number of
items to be analyzed is not particularly limited, however, it is
usually between 1 and 20, preferably between 3 and 5. In this case,
various number of analytical sections, bypass channels and drawing
channels may be formed depending upon the number of the items to be
analyzed.
[0125] An analysis using such a device for multiple analysis may be
performed, for example, as follows.
[0126] First, a portion of the covering 5 corresponding to the
suction pressure generating chamber 1 of the device is compressed
by applying a pressure, for example, by pressing with a finger.
Then, in this state, the opening 4 at the end of the protrusion
portion is contacted with a sample. Then, the pressure applied to
the chamber is released by weakening the force of pressing with a
finger so that the compressed portion of the covering can return to
its original shape due to the elasticity of the covering. At this
time, a suction pressure is developed, whereby the sample is drawn
into the opening 4 and then further drawn through the three drawing
channels 2a into the respective three analytical sections 3. By
having the bypass channel 6 and providing the relationship of the
three liquid flow resistances (X,Y,Z) of X>Y>Z in this
device, even if excess suction pressure is generated, the sample is
ensured to be introduced into the analytical sections 3, where the
sample undergoes reaction with a reagent. In addition, a
possibility that a generated pigment might flow into the suction
pressure generating chamber 1 can be eliminated. Then, the device
in which a color is developed in the reagent film is set in a
predetermined position in an optical measuring apparatus such as a
densitometer. Then, light is irradiated into the device, so that
when using the densitometer, a reflected light is detected in a
detecting section to measure the developed color, so that three
items can be analyzed simultaneously.
EXAMPLE 6
[0127] FIG. 8 shows a plan view of an embodiment of a device for
analyzing a sample in which a portion of a drawing channel between
an opening and a branching portion of a bypass channel snakes and
also has a small diameter, so that the liquid stress in the portion
of the drawing channel becomes the largest.
[0128] As shown in the drawing, this device comprises an
approximately rectangular plate shaped body 5 whose one end portion
is decreasing in width toward the end, and the body 5 comprises a
base member and a covering which covers over the surface of the
base member.
[0129] Then, in the upper surface of the base member, a suction
pressure generating chamber 1 is formed in a portion on the other
end side (right side in the drawing) relative to the center of the
body 5, from which a drawing channel 2b extends toward the one end
portion of the body having decreasing width. An analytical section
3 is formed in a certain position in the drawing channel 2b (in an
approximately center portion of the body 5). Then, a drawing
channel 2a extends from the analytical section 3 toward the portion
of the body having decreasing width, and the drawing channel 2a
snakes from a certain point. Furthermore, a bypass channel 6
branches from the drawing channel 2a, and it is brought to be
communicated with the suction pressure generating chamber 1.
Furthermore, as previously described, the drawing channel 2a snakes
from the branching portion of the bypass channel 6, and the end of
the drawing channel 2a is formed into a funnel-shaped opening 4 on
the end portion of the body having decreasing width. A reagent is
disposed in the analytical section 3, and when the covering is
transparent, the reagent is disposed by sticking a reagent film
containing the reagent on a portion of the inner surface of the
covering corresponding to the analytical section 3.
[0130] The whole portion of the drawing channel 2a between the
branching portion of the bypass channel 6 and the analytical
section 3 is made to have a large diameter, and a portion 6a of
certain length from the branching portion of the bypass channel 6
is made to have a small diameter, and the whole drawing channel 2b
is made to have a small diameter. The snaking portion of the
drawing channel 2a is made to have a small diameter and to be
longer than the drawing channel 2b. Thus, the liquid flow
resistance (W) in the snaking portion of the drawing channel 2a is
larger than the liquid flow resistance (X) in the drawing channel
2b. Accordingly, the relationship of the four liquid flow
resistances, namely, the liquid flow resistance (W) in the snaking
portion of the drawing channel 2a, the liquid flow resistance (X)
in the drawing channel 2b, the liquid flow resistance (Y) in the
bypass channel 6, and the liquid flow resistance (Z) in a portion
of the drawing channel 2a between the branching portion of the
bypass channel 6 and the analytical section 3 is such that
W>X>Y>Z.
[0131] In such a device, the snaking portion of the drawing channel
2a is usually 5 to 15 mm in overall length, 0.1 to 0.5 mm in width,
and 0.1 to 0.5 mm in depth. Other things such as materials, the
dimensions of the suction pressure generating chamber and other
portions of the drawing channels, and the like are the same in this
device as those in the predescribed embodiment.
[0132] Next, an analysis using such a device is performed, for
example, as follows.
[0133] First, a portion of the covering 5a corresponding to the
suction pressure generating chamber 1 of the device is compressed
by applying a pressure, for example, by pressing with a finger.
Then, in this state, the opening 4 at the end of the protrusion
portion is contacted with a sample. Then, the pressure applied to
the chamber is released by weakening the force of pressing with a
finger, so that the compressed portion of the covering 5a can
return to its original shape due to the elasticity of the covering.
At this time, a suction pressure is developed, whereby a sample is
drawn into the opening 4. Because the relationship of the four
liquid flow resistances (W, X, Y, Z) is W>X>Y>Z, even if a
strong suction pressure is developed, it is ensured that the sample
is further introduced into the analytical section 3, where the
sample is analyzed. Furthermore, because the liquid flow resistance
(W) in the snaking portion of the drawing channel 2a is the
largest, possibilities that the sample introduced into the
analytical section 3 and/or a generated pigment might flow out
toward the side of the opening 4 is reduced. Then, the device in
which a color is developed in the reagent film is set in a
predetermined position in an optical measuring apparatus such as a
densitometer. Then, light is irradiated into the device from the
upper surface side of the body 5, so that when using the
densitometer, a reflected light is detected in a detecting section
to measure the developed color.
EXAMPLE 7
[0134] FIG. 9 shows an embodiment of a device for analyzing a
sample of the present invention. FIG. 9(A) is a plan view of such a
device, and FIG. 9(B) is a cross-sectional view of the device of
FIG. 9(A) taken along the line III-III. As shown in the drawings,
this device is formed by lamination of a plurality of films, and
the body of the device is an approximately rectangular plate
shaped.
[0135] In this device, a suction pressure generating chamber 1 is
formed as a protrusion in a portion of one end side (right side in
the drawings) relative to center of the approximately rectangular
plate shaped body. A drawing channel 2 extends from under side of
the suction pressure generating chamber 1 toward the end opposite
to the suction pressure generating chamber 1 (the other end) of the
approximately rectangular plate shaped body. An analytical section
3 is formed in a certain position in the drawing channel 2, and the
end of the drawing channel 2 communicates with the opening 4 formed
in the other end of the approximately rectangular plate shaped body
through a liquid pooling portion 9. A window 10 is formed under the
analytical section 3, if the need arises. For example, if using
glucose oxidase (GOD) as a reagent, because the reagent requires
oxygen for coloring reaction, the window should be formed for
supplying oxygen. However, except in such a case, when the portion
of the film corresponding to the analytical section 3 is
transparent so that light can enter into the analytical section 3,
it is not required to form the window. Furthermore, a reagent film
7 impregnated with a reagent is disposed under the analytical
section 3, so that it covers the window 10. Furthermore, a stopper
which is gas-permeable and liquid-impermeable 8 is formed in a
certain position in the drawing channel 2b between the suction
pressure generating chamber 1 and the analytical section 3 on the
side of the suction pressure generating chamber 1. The stopper 8 is
formed by disposing a hydrophobic porous film in a certain position
in the drawing channel 2b.
[0136] Furthermore, an air vent passage 25 branches from a portion
of the drawing channel 2a between the liquid pooling portion 9 and
the analytical section 3, and the end 26 of the passage is open to
the outside of the body. By providing such an opening, capillarity
can be developed because of the air vent passage 25.
[0137] Furthermore, the area of the cross section of the air vent
passage 25 is made smaller than that of the cross section of the
liquid pooling portion 9, so that the liquid flow resistance in the
air vent passage 25 is larger than that in the liquid pooling
portion 9. Specifically, the liquid pooling portion 9 is about four
times as wide as the drawing channel 2 or the air vent passage 25,
and the liquid pooling portion 9 is about twice as thick as the
drawing channel 2 or the air vent passage 25.
[0138] Such a device of laminated films can be produced, for
example, by laminating films 11, 12, 13, and 14 formed into
respective types of shapes, with a reagent film 7 and a hydrophobic
porous film 8 placed therebetween, as shown in FIG. 10.
[0139] The film 14 is to be the under surface of the device,
wherein the window 10 is provided. In the film 13 are formed
cut-out portions to form the liquid pooling portion 9, the air vent
passage 25, the analytical section 3, and the drawing channel 2,
respectively. The film 12 ensures the thickness of the liquid
pooling portion 9 (the size of the cross-sectional area of the
portion). In the film 12 are formed a cut-out portion in order to
form the liquid pooling portion 9, a circular shaped cut-out
portion in order to form an opening at the end of the air vent
passage 25, and a circular shaped cut-out portion in order to
communicate the drawing channel 2b with the suction pressure
generating chamber 1. In the film 11 are formed a protrusion of an
approximately cylindrical convex portion in order to form the
suction pressure generating chamber 1 and a circular cut-out
portion in order to form an opening at the end of the air vent
passage 25.
[0140] Then, the reagent film 7 is disposed in a portion between
the film 14 and the film 13 where the analytical section 3 is to be
formed, and the hydrophobic porous film 8 is disposed between the
film 13 and the film 12 in a portion to be a part of the drawing
channel 2b. In this state, the four films 14, 13, 12, and 11 are
laminated in this order from the bottom and then integrated
together to produce a device as shown in FIG. 9.
[0141] An example of the hydrophobic porous film is a hydrophobic
resin porous film, specifically, a polyethylene porous film, a
polypropylene porous film, a Teflon porous film, or the like.
Suitable hydrophobic resin porous films are Celgard (Product
Name/Hoechst Celanese Co., Ltd.), and Hipore (Product Name/Asahi
Chemical Industry Co., Ltd.). The average diameter of a pore in the
hydrophobic resin porous film is usually from 0.1 to 1 .mu.m,
preferably from 0.3 to 0.7 .mu.m. Furthermore, the thickness of the
hydrophobic resin porous film is usually from 10 to 100 .mu.m. Such
a hydrophobic resin porous film can be produced, for example, by
forming a film using said hydrophobic resin and then orienting the
film either uniaxially or biaxially.
[0142] The reagent film 7 is a film impregnated with a reagent, and
the type of the reagent is selected as appropriate depending upon
the type of the object for analysis. The structure of the reagent
film is also determined as appropriate depending upon the type of
the object to be analyzed. For example, when plasma components of
blood is the object for analysis, the reagent film usually has a
structure in which a filtration layer for separating blood cells, a
reagent layer impregnated with a reagent, and a base member are
laminated in this order. Then, the reagent film 7 is arranged in
the analytical section 3 so that the filtration layer can contact
with blood (a liquid sample). Moreover, conventionally known
materials can be applied for the respective layers in the reagent
film.
[0143] When producing a device of the present invention, the films
may be integrated by using an adhesive to bond the respective films
to each other or by laminating the films by pressing or
heating.
[0144] Furthermore, suitable materials for the films which comprise
the device are, for example, polyethylene, polyethylene
terephthalate (PET), polystyrene, polyvinyl chloride, and the like,
and particularly PET is desired because of processability.
[0145] The dimensions of the device shown in FIG. 9 are usually 15
to 60 mm in length, 5 to 20 mm in width, and 1 to 3 mm in
thickness. Furthermore, the dimensions of the suction pressure
generating chamber 1 are usually 3 to 15 mm in diameter and 0.5 to
3 mm in height. Furthermore, the dimensions of the drawing channel
2 are usually 10 to 40 mm in overall length, 0.5 to 2 mm in width,
and 0.1 to 0.5 in thickness, wherein the drawing channel 2a is 5 to
30 mm in length, and the drawing channel 2b is 5 to 30 mm in
length. Furthermore, the dimensions of the analytical section 3 are
usually 2 to 10 mm in diameter and 0.1 to 1 mm in height. The
dimensions of the liquid pooling portion 9 are usually 2 to 10 mm
in length, 2 to 10 mm in width, and 0.2 to 1 mm in thickness. The
dimensions of the air vent passage 25 are usually 2 to 10 mm in
overall length, 0.5 to 2 mm in width, 0.1 to 0.5 mm in thickness,
and 0.5 to 5 mm in diameter of the opening of the passage. The
dimensions of the opening 4 are usually 2 to 10 mm in width and 0.2
to 1 mm in thickness.
[0146] Next, a method for analyzing a sample using the device shown
in FIG. 9 will be described by referring to FIG. 11. In FIG. 11,
the same parts as shown in FIG. 9 are referred to by using the same
signs.
[0147] First, the protruding suction pressure generating chamber 1
in the device is compressed by applying pressure, for example, by
pressing with a finger. Then, in this state, the opening 4 is
contacted with a sample 15 in a predetermined sampling spot. Then,
as shown in FIG. 11(A), the sample 15 is drawn by capillarity
developed due to the air vent passage 25 into the opening 4 and
retained in the liquid pooling portion 9. Then, the opening 4 is
detached from the sampling spot, and then the force of pressing
with a finger is weakened to release the applied pressure. Then,
the compressed suction pressure generating chamber 1 returns to the
original shape due to the elasticity, whereby a suction pressure (a
negative pressure) is developed. Due to the developed suction
pressure, the sample is retained in the liquid pooling portion 9 is
drawn through the drawing channel 2a into the analytical section 3
as shown in FIG. 11(B). The time period required for introducing
the sample into the analytical section 3 in such a method is
markedly short compared to the time required for drawing a sample
by using capillarity. In addition, such a drawing process is hardly
affected by properties of the sample such as viscosity.
Furthermore, in this drawing process, because the liquid stresses
in the liquid pooling portion 9 and the air vent passage 25 are
adjusted as described above, a part of the sample 15 remains in the
air vent passage 25 as shown in the drawing, so that air inclusion
can be prevented. Furthermore, even if excess suction pressure is
developed, because the stopper 8 is formed, it is ensured that the
sample 15 is introduced into the analytical section 3 without
causing a flow of the sample 15 into the suction pressure
generating chamber 1. Accordingly, it is not necessary to take care
in adjusting the pressing force with a finger. Then, in the
analytical section 3, a reaction between a component in the sample
15 and the reagent contained in the reagent film 7 takes place to
generate a pigment, whereby a color is developed in the reagent
film 7. Then, the device in which a color is developed in the
reagent film 7 is set in a predetermined position in an optical
measuring apparatus such as a densitometer. Then, light is
irradiated into the device through the window 10 formed in the
under surface of the device, so that when using the densitometer, a
reflected light is detected in a detecting section to measure the
color developed in the regent film. Furthermore, in this measuring,
when both the whole analytical section 3 and the reagent film 7 are
transparent, analysis can also be conducted by using a transmitted
light.
EXAMPLE 8
[0148] FIG. 12 shows a plan view of an embodiment of a device for
multiple analysis provided with a plurality of analytical sections
arranged in series.
[0149] As shown in the drawing, this device is provided with three
analytical sections 3 in certain positions in a drawing channel 2,
and a reagent film 7 is disposed in each of the analytical sections
3. The respective reagent films 7 are impregnated with different
types of reagents. The structure of the device other than these
aspects is the same as that of the device shown in FIG. 9, and the
same parts as in FIG. 9 are referred to by using the same
signs.
[0150] This device can be produced by laminating a plurality of
films having predetermined shapes and then integrating them
together, as in the predescribed device in Example 7, and the
method for producing the device, used materials, and the like are
also the same as in the device in Example 7. Furthermore, the
overall dimensions of the device are usually 15 to 100 mm in
length, 5 to 20 mm in width, and 1 to 3 mm in thickness.
Furthermore, the whole length of the drawing channel 2 is usually
20 to 80 mm, and the spacing between the analytical sections is
usually 3 to 10 mm. The dimensions in other parts of the device are
the same as in the device of Example 7.
[0151] Although a device provided with three analytical sections is
described in this embodiment, the present invention is not limited
to such a device, and any number of analytical sections can be
provided depending upon the desired number of items for
measurement.
[0152] Next, a method for analysis using such a device for multiple
analysis is performed, for example, as follows.
[0153] First, a suction pressure generating chamber 1 of the device
is compressed by pressing as in the predescribed embodiment. Then,
in this state, the opening 4 is contacted with a sample in a
predetermined sampling spot, whereby the sample is drawn by
capillarity into the liquid pooling portion 9 where it is retained.
Then, the opening 4 is detached from the sampling spot, and
thereafter the pressure applied to the suction pressure generating
chamber 1 is released, so that a suction pressure is developed.
Accordingly, the sample is introduced into the respective three
analytical sections 3 one after another, where respective reactions
between compounds in the sample and the reagents contained in the
respective reagent films 7 take place. Then, the device is set in a
predetermined position in an optical measuring apparatus capable of
performing multiple analysis. Then, light is irradiated through the
window formed in the under surface of the device, whereby the
colors developed in the respective reagent films 7 are measured. An
example of the optical measuring apparatus is a densitometer. Thus,
by using such a device for multiple analysis, a plurality of items
can be measured simultaneously.
EXAMPLE 9
[0154] FIG. 13 shows a plan view of a device for analyzing a sample
for multiple analysis provided with a plurality of analytical
sections arranged in parallel.
[0155] As shown in the drawing, this device has three drawing
channels 2. An analytical section 3 is formed in each of the
drawing channels 2, where a reagent film 7 is disposed. Each
reagent film 7 is impregnated with a type of reagent different to
each other. The portions of each of the three respective drawing
channels 2 which extend from the three respective analytical
sections 3 toward the opening 4 merge to form a drawing channel 2a
in a certain position before reaching the liquid pooling portion 9.
Furthermore, three drawing channels 2b extend from a suction
pressure generating chamber 1 and are in communication with the
three analytical sections 3, respectively. This device and the
device shown in FIG. 9 in Example 7 have the same structure other
than these characteristics, therefore, the same parts are referred
to by using the same signs.
[0156] This device can be produced by laminating a plurality of
films having predetermined shapes and then integrating them
together, as in the predescribed device in Example 7, and the
method for producing the device, the materials used, and the like
are also the same as those in Example 1. Furthermore, the overall
dimensions of the device are usually 15 to 60 mm in length, 10 to
50 mm in width, 1 to 3 mm in thickness. Furthermore, the overall
length of the drawing channel 2 is usually 10 to 40 mm, and the
spacing of the analytical sections 3 to each other is usually 3 to
10 mm. The dimensions of other parts of the device are the same as
in the device of Example 7.
[0157] Although a device provided with three analytical sections is
shown in this embodiment, the present invention is not limited to
this device, and any number of analytical sections and drawing
channels can be provided depending upon the desired number of items
for measurement.
[0158] Next, an analysis using such a device for multiple analysis
is performed, for example, as follows.
[0159] First, a suction pressure generating chamber 1 of the device
is compressed by pressing as in the predescribed embodiment. In
this state, the opening 4 is contacted with a sample in a
predetermined sampling spot, and the sample is introduced by
capillarity into the liquid pooling portion 9, where it is
retained. Then, the opening 4 is detached from the sampling spot,
and thereafter the pressure applied to the suction pressure
generating chamber 1 is released so that a suction pressure is
developed. As a result, the sample is introduced into each of the
three analytical sections 3 simultaneously, where reactions between
components in the sample and the reagents contained in the
respective reagent films 7 take place. Then, the device is set in a
predetermined position in an optical measuring apparatus capable of
performing multiple analysis. Then, light is irradiated through the
window formed in the under surface of the device, whereby the color
developed in the respective reagent films 7 is measured.
[0160] Thus, by using such a device for multiple analysis, a
plurality of items can be measured simultaneously. An example of
the optical measuring apparatus is a densitometer.
[0161] Having described the devices for multiple analysis in
Example 8 and Example 9, whether the analytical sections are
arranged either in series or in parallel may be determined by
various conditions such as influence of the reagents to each other,
the shapes of the device, or the like.
EXAMPLE 10
[0162] FIG. 14 shows a plan view of a device for analyzing a sample
in which a reagent positioning section, reagent reaction section,
and a measuring section are provided independently in certain
positions in the drawing channel.
[0163] As shown in the drawing, this device is provided with a
reagent positioning section 32, a reagent reaction section 30, and
a measuring section 31, each of them being formed in a certain
position in a drawing channel 2. The shape of the drawing channel
does not particularly change due to the reagent positioning section
32, and a reagent is simply disposed in the drawing channel. Also,
it may be a depressed cylindrical shaped cavity like the reagent
reaction section. Moreover, the reagent can be disposed by simply
positioning the reagent in the channel, or attaching the reagent to
the reagent positioning section by using a hydrophilic polymer or
the like. Examples of the reagents include wet-type reagents or the
like capable of moving together with a sample. More particularly,
example of such reagents are, GOD, peroxidase (POD),
4-aminoantipyrine,
N-ethyl-N-(2-hydroxyne-3-sulfopropyl)-3-methylaniline (TOOS) and
the like. Moreover, even a dry-type reagent can move together with
a sample if it can be dissolved in a sample. Furthermore, the
reagent reaction section 30 is formed in a same way as in the
predescribed embodiment other than that a reagent film is not
disposed therein. Furthermore, the measuring section 31 is formed
into a depressed cylindrical shaped cavity like the reagent
reaction section 30, except that it is made transparent for
permitting light entrance. Moreover, an absorbent member such as a
filter paper may be disposed in the measuring section 31 in order
to fix the transferred pigment. This device and the device shown in
FIG. 9 in Example 7 have the same structure other than these
characteristics, therefore the same parts are referred to by using
the same signs. Moreover, the reagent reaction section 30 may also
serve as a measuring section like in Example 7, and in such a case,
the reagent reaction section 30 is made transparent for permitting
light entrance.
[0164] This device for analyzing a sample can be produced by
laminating a plurality of films having predetermined shapes and
then integrating them together, as in the predescribed embodiment
in Example 7. In addition, the method for producing such a device,
the materials used, and the like are also the same as those in
Example 7. Furthermore, generally a reagent is prepositioned by
using a hydrophilic polymer or the like during lamination process
of the films. Furthermore, the overall dimensions of the device are
usually 15 to 100 mm in length, 5 to 20 mm in width, and 1 to 3 mm
in thickness. Furthermore, the overall length of the drawing
channel 2 is usually 20 to 80 mm, and the spacing between the
reagent positioning section, the reagent reaction section 30, and
the measuring section 31 to each other is usually 3 to 10 mm. The
dimensions of other parts of the device are the same as in the
embodiment in Example 7.
[0165] Next, an analysis using such a device for multiple analysis
is performed, for example, as follows.
[0166] First, a suction pressure generating chamber 1 is compressed
by pressing as in the predescribed embodiment. In this state, the
opening 4 is contacted with a sample in a predetermined sampling
spot, and the sample is drawn by capillarity into the liquid
pooling portion 9, where it is retained. Then, the opening 4 is
detached from the sampling spot, and thereafter the pressure
applied to the suction pressure generating chamber 1 is released so
that a suction pressure is developed. As a result, the sample is
transferred into the reagent positioning section 32, into the
reagent reaction section 30, and then into the measuring section 31
in this order. Then, the sample first moves into the reagent
reaction section 30 with the reagent present in the reagent
positioning section 32, where a reaction between a component in the
sample and the reagent takes place to generate a pigment. The
pigment may be produced in a portion between the reagent reaction
section 30 and the measuring section 31. Then, the pigment moves to
the measuring section 31. If a filter paper is positioned in the
measuring section 31, a color is developed in the filter paper.
Then, the device is set in a predetermined position in an optical
measuring apparatus. Then, light is irradiated into the measuring
section, whereby the color of the pigment or the color developed in
the filter paper is measured by using an optical measuring
apparatus such as a densitometer. As a condition of this
measurement, when using the predescribed reagents such as GOD, this
measuring should be performed one minute after the reaction with a
wavelength of 570 nm.
EXAMPLE 11
[0167] FIG. 15 shows a plan view of a device for analyzing a sample
in which two reagent positioning sections are provided in certain
positions in the drawing channel.
[0168] As shown in the drawing, this device is provided with a
first reagent positioning section 32a and a second reagent
positioning section 32b formed in certain positions in a drawing
channel 2, the two sections forming the reagent reaction section
30, and further provided with a measuring section 31. Usually, a
first reagent is disposed in the first reagent positioning section
32a, and a second reagent is disposed in the second reagent
positioning section 32b.
[0169] Although the first reagent positioning section 32a and the
second reagent positioning section 32b are formed into depressed
cylindrical shaped cavities, reagents may be simply disposed in the
drawing channel 2 without changing the shape of the channel, as
described later. Furthermore, in disposing the reagents, the
reagents may be attached to the reagent positioning sections by
using a hydrophilic polymer or the like, while it may be simply
positioned as in the predescribed device in Example 10. Suitable
reagents are those comprising two or more components which cannot
be mixed prior to a reaction with a sample, as previously
described. An example of such a reagent is an enzyme-substrate type
reagent, specifically, trypsin-substrate type reagent. The
substrate usually generates a pigment through an enzyme reaction.
Furthermore, when dissolved and mixed in a sample, this reagent is
capable of moving.
[0170] Also, the measuring section 31 is formed as a depressed
cylindrical shaped cavity like the reagent positioning section.
Further, an absorbent member such as a filter paper may be disposed
in the measuring section 31 in order to fix the transferred
pigment. This device and the device shown in FIG. 9 in Example 7
have the same structure other than these characteristics,
therefore, the same parts are referred to by using the same signs.
Moreover, a reagent reaction section may serve as a measuring
section like in Example 7. In case of this embodiment, the second
positioning disposed section 32b may serve as the measuring section
31.
[0171] This device can be produced by laminating a plurality of
films having predetermined shapes and then integrating them
together, as in the predescribed device in Example 7. In addition,
the method for producing such a device, the materials used, and the
like in this device are also the same as those in Example 7.
Furthermore, generally a reagent is prepositioned by using a
hydrophilic polymer or the like during lamination process of the
films. Furthermore, the overall dimensions of the device are
usually 15 to 100 mm in length, 5 to 20 mm in width, and 1 to 3 mm
in thickness. Furthermore, the overall length of the drawing
channel 2 is usually 20 to 80 mm, and the spacing between the
reagent positioning sections and the measuring section is usually 3
to 10 mm. The dimensions of other parts of the device are the same
as in Example 7.
[0172] Next, an analysis using this device is performed, for
example, as follows.
[0173] First, as in the predescribed embodiment, a suction pressure
generating chamber 1 is compressed by applying pressure. In this
state, the opening 4 is contacted with a sample in a predetermined
sampling spot, and the sample is drawn by capillarity into the
liquid pooling portion 9 to be retained. Then, the opening 4 is
detached from the sampling spot, and then the pressure applied to
the suction pressure generating chamber 1 is released so that a
suction pressure is developed. As a result, the sample is
transferred into the first reagent positioning section 32a, into
the second reagent positioning section 32b, and into the measuring
section 31 in this order. Then, the sample first moves into the
second reagent positioning section 32b with the first reagent
present in the first reagent disposed section 32a, where the three
of the sample, the first reagent, and the second reagent are
reacted to each other to generate a pigment. The pigment may be
generated in a portion between the second reagent disposed section
32b and the measuring section 31. Then, the pigment moves to the
measuring section 31. When a filter paper is positioned in the
measuring section 31, a color is developed in the filter paper.
Then, the device is set in a predetermined position in an optical
measuring apparatus. Then, light is irradiated into the measuring
section 31, whereby the color of the pigment or the color developed
in the filter paper is measured by using an optical measuring
apparatus such as a densitometer.
EXAMPLE 12
[0174] FIG. 16 shows a plan view of a device for analyzing a sample
in which three reagent positioning sections and a measuring section
are provided in certain positions in a drawing channel. This device
has a structure in which those in Example 10 and 11 are
integrated.
[0175] As shown in the drawing, this device is provided with a
first reagent positioning section 32a, a second reagent positioning
section 32b, and a third reagent positioning section 32c formed in
certain positions in a drawing channel 2, all of these forming a
reagent reaction section 30 in combination, and further provided
with a measuring section 31 formed in a certain position in the
drawing channel 2. Usually, a first reagent is disposed in the
first reagent positioning section 32a, a second reagent is disposed
in the second reagent positioning section 32b, and a third reagent
is disposed in the third reagent positioning section 32c.
[0176] The reagents are simply disposed in the respective three
reagent positioning sections 32a, 32b, and 32c without changing the
shape of the drawing channel 2. Furthermore, in disposing the
reagents, they may be simply disposed in the drawing channel as in
the device previously described in Example 4, or alternatively, the
reagents may be attached to the respective reagent positioning
sections by using a hydrophilic polymer or the like. Suitable
reagents are those comprising two or more components which cannot
be mixed prior to a reaction with a sample as previously described.
Examples of such a reagent include enzyme-substrate type reagents,
for example, a reagent comprising a trypsin, the substrate of the
trypsin, and a buffer solution. By using such a reagent, for
example, a trypsin inhibitor in urine can be measured. Furthermore,
a pigment is generated through a reaction between the substrate and
the enzyme. With regard to this reagent, the first reagent is the
buffer solution, the second reagent is the trypsin, and the third
reagent is the substrate. Besides, when dissolved and mixed in a
sample, this reagent is capable of moving.
[0177] The measuring section 31 is formed as a depressed
cylindrical shaped cavity. An absorbent member such as a filter
paper may be disposed in the measuring section 31 in order to fix
the transferred pigment. The structure of this device other than
these characteristics is the same as that of the device shown in
FIG. 9 in Example 7, therefore the same parts are referred to by
using the same signs.
[0178] This device can be produced by laminating a plurality of
films having predetermined shapes and then integrating the films
together, as in the device described in Example 7. In addition, the
method for producing such a device, the materials used, and the
like are also the same as those in Example 7. Furthermore, the
reagents are generally disposed in advance by using hydrophilic
polymers or the like during the process of laminating the films.
Furthermore, the overall dimensions of the device are usually 15 to
100 mm in length, 5 to 20 mm in width, and 1 to 3 mm in thickness.
Furthermore, the whole length of the drawing channel 2 is usually
20 to 80 mm, and the spacing between the reagent positioning
sections and the measuring section is usually 3 to 10 mm. The
dimensions of other parts of the device are the same as in Example
7.
[0179] Next, a method for analyzing a sample by using this device
will be described by referring to a case using the predescribed
reagent comprising a buffer solution, a trypsin and a
substrate.
[0180] First, the device for analyzing a sample having a buffer
solution in the first reagent positioning section 32a, a trypsin in
the second reagent positioning section 32b, and a substrate in the
third reagent positioning section 32c is prepared. Then, as in the
predescribed embodiment, a suction pressure generating chamber 1 is
compressed by applying a pressure, and in this state, the opening 4
is contacted with a sample (urine) in a predetermined sampling
spot, so that the sample is drawn by capillarity into the liquid
pooling portion 9 to be retained. Then, the opening 4 is detached
from the sampling spot, and then the pressure applied to the
suction pressure generating chamber 1 is released so that a suction
pressure is developed. As a result, the sample is transferred into
the first reagent positioning section 32a, into the second reagent
positioning section 32b, into the third reagent positioning section
32c, and into the measuring section 31 in this order. Then, the
sample moves into the second reagent positioning section 32b with
the buffer solution present in the first reagent positioning
section 32a, where the sample, the buffer solution, and the trypsin
are mixed together. Then, the mixture is transferred into the third
reagent positioning section 32c, where it is mixed with the
substrate, whereby an enzyme reaction is caused to generate a
pigment. Moreover, the pigment may be generated in a position
between the third reagent positioning section 32c and the measuring
section 31. Then, the pigment moves to the measuring section 31.
Therefore, when a filter paper is positioned in the measuring
section 31, a color is developed in the filter paper. Then, the
device is set in a predetermined position in an optical measuring
apparatus. Then, light is irradiated into the measuring section 31,
whereby the color of the pigment or the color developed in the
filter paper is measured by using an optical measuring apparatus
such as a densitometer.
EXAMPLE 13
[0181] Next, an embodiment of a device for analyzing a sample of
the present invention in which a vent is formed in a suction
pressure generating chamber will be described.
[0182] FIG. 17 shows a cross-sectional view of an embodiment of
this device. As shown in FIG. 17(A), the basic structure of the
device is the same as that of the device shown in FIG. 9 in Example
7, and the same parts are referred to by using the same signs. The
vent 1a is usually 0.1 to 5 mm in diameter. An analysis of a sample
by using this device is conducted, for example, as follows.
[0183] First, the opening 4 of the device is contacted with a
sample, so that the sample 15 is retained in the liquid pooling
portion 9. Then, as shown in FIG. 17(B), the suction pressure
generating chamber 1 is pressed with a finger or the like. At this
time, because the air in the suction pressure generating chamber 1
is discharged through the vent la, the sample is not discharged
through the opening 4 by the air forced from the suction pressure
generating chamber 1. Then, as shown in FIG. 17(C), the vent 1a is
closed with a finger or the like when the suction pressure
generating chamber 1 is compressed. Then, when the pressure applied
to the suction pressure generating chamber 1 is released in a state
in which the vent 1a is closed as shown in FIG. 17(D), the suction
pressure generating chamber 1 returns to its original shape and
thereby a suction pressure is developed. As a result, the sample 15
is transferred through the drawing channel 2 into the analytical
section 3. The subsequent analyzing operation is the same as in
Example 7.
[0184] Accordingly, by using such a device in which the suction
pressure generating chamber 1 is provided with the vent la, it is
possible to apply a pressure to the suction pressure generating
chamber 1 after the opening 4 is contacted with the sample 15 and
the sample is retained in the liquid pooling portion. As a result,
sampling can be performed easily.
EXAMPLE 14
[0185] Next, an embodiment of a device of the present invention in
which a suction pressure generating tube is used as a suction
pressure generating means will be described.
[0186] FIG. 18 shows a cross-sectional view of an embodiment of
such a device for analyzing a sample. As shown in FIG. 18(A), this
device has the same structure as that of the device shown in FIG. 9
in Example 7, except that a suction pressure generating tube 21 is
provided in place of a suction pressure generating chamber, and the
same parts are referred to by using the same signs. The suction
pressure generating tube 21 can be formed, for example, by placing
a resin sheet, which is bent so that the shape of a cross-section
of the sheet in longitudinal direction becomes approximately a
reverse U-shaped, on the body of the device. In this case, one end
of the suction pressure generating tube communicates through a
stopper 8 which is gas-permeable and liquid-impermeable with the
drawing channel 2, and the other end is closed. In the suction
pressure generating tube, usually the sheet is 0.01 to 2 mm in
thickness, and the tube is 0.5 to 5 mm in height on the inside, 1
to 10 mm in width on the inside, and 5 to 30 mm in length. It is
desired that the suction pressure generating tube 21 is formed so
that it may not overlap with the drawing channel 2, an analytical
section 3, or the like. This is because it is necessary to compress
the tube by applying a pressure through a hand in order to develop
a suction pressure by the suction pressure generating tube 21, and
there is a possibility that the shape of the drawing channel or the
like might be changed by the pressure. Suitable materials for the
resin sheet are, for example, soft vinyl chloride resin, soft
silicon resin, natural rubber, and the like. Furthermore, the shape
of a cross section of the suction pressure generating tube in a
longitudinal direction is not limited to said reverse U-shape. For
example, it may be rectangular or the like.
[0187] A sample may be analyzed by using this device, for example,
as in the following steps. First, the opening 4 of the device is
contacted with a sample, so that the sample 15 is retained in a
liquid pooling portion 9. Then, as shown in FIG. 18(B), a portion
of the suction pressure generating tube 21 on one end side (right
end in the drawings) in communication with the drawing channel 2 is
pressed with a finger or the like, whereby the corresponding
portions of the sheet are adhered to each other. Then, as shown in
FIG. 18(C) and FIG. 18(D) successively, the tube can be drawn by
moving the pressing portion toward the open end. As a result, a
suction pressure is developed in the suction pressure generating
tube 21, whereby the sample 15 is moved through the drawing channel
2 into the analytical section 3. Subsequent analyzing operation is
conducted in the same way as in Example 7.
[0188] Accordingly, by using such a device having the suction
pressure generating tube as the suction pressure generating means,
a sucking operation can be performed after the opening 4 is
contacted with the sample 15, which is then retained in the liquid
pooling portion, as in the device provided with a suction pressure
generating chamber having the vent la. As a result, sampling can be
operated more easily.
EXAMPLE 15
[0189] Next, an embodiment of the present invention where a sample
is analyzed by an electrochemical means will be described.
[0190] FIG. 19 shows a device for analyzing a sample provided with
electrodes. FIG. 19(A) is a plan view of the device, and FIG. 19(B)
is a cross-sectional view of the device shown in FIG. 19(A) taken
along the line IV-IV. The device shown in these drawings has the
same structure as the device in Example 7, except that the
electrodes are formed and no window is formed, therefore the same
parts are referred to by using the same signs.
[0191] As shown in the drawings, the electrodes comprise a working
electrode 33a and a counter electrode 33b, which are formed under
the analytical section 3. Both of the electrodes extend beyond the
suction pressure generating chamber 1, and the ends of them are
formed into terminals 33c and 33d, respectively.
[0192] This device can be produced by laminating the films formed
into respective predetermined shapes as in Example 7. For example,
as shown in FIG. 20, the device can be produced by laiminating
films 11, 12, 13, and 14 formed into respective types of shapes,
with a reagent film 7 and a hydrophobic porous film 8 positioned
therebetween.
[0193] The film 14 forms the under side portion of the device, and
the electrodes (33a, 33b, 33c, 33d) are formed on the upper surface
of the film. The electrodes can be formed, for example, by printing
the terminals (33c and 33d) on the film by screen printing using
silver (Ag) paste, while printing the working electrode 33a and the
counter electrode 33b by screen printing using conductive carbon
paste. The dimensions of the electrodes are, for example, in case
of the shape shown in the drawing, usually 1 to 14 mm in outer
diameter of the working electrode 33a, 3 to 15 mm in outer diameter
of the counter electrode 33b, and 0.5 to 2 mm in width of the
spacing between these electrodes. Furthermore, the overall length
of the electrode including the terminals is 10 to 50 mm. Moreover,
the shapes of the electrodes are not limited to the shapes shown in
the drawing. The material for the film is not particularly limited
as long as it has insulating property, and for example, PET,
polypropylene, polyester or the like may be used. Furthermore, a
hole to form a window is not formed in the film 14. Furthermore,
the film 14 is not necessarily transparent, and it may be
colored.
[0194] In producing this device, a reagent film 7 produced
independently may be used, or alternatively, the reagent film 7 may
be directly formed on the electrodes (the working electrode and the
counter electrode). For example, the reagent film can be formed by
applying a hydrophilic high polymer aqueous solution on the
electrodes portion followed by drying, thereupon further applying a
reagent solution followed by drying. An example of the high polymer
aqueous solution is a 0.5% by weight aqueous solution of
carboxymethyl cellulose. In case of analyzing lactic acid, for
example, a suitable reagent solution is 400 U/ml of lactate oxidase
and 2.0% by weight aqueous solution of potassium ferricyanide.
Furthermore, in case of analyzing glucose, glucose oxidase may be
used in place of said lactate oxidase, and in case of analyzing
cholesterol, cholesterol oxidase may be used in place of said
lactate oxidase.
[0195] Next, a method for analyzing a sample by using this device
will be described. First, as in the predescribed embodiments, the
suction pressure generating chamber 1 is compressed, and in this
state, the opening 4 is contacted with a sample in a predetermined
sampling spot, thereby the sample is drawn by capillarity into the
liquid pooling portion 9 to be retained. Then, the pressure applied
to the suction pressure generating chamber 1 is released to develop
a suction pressure, whereby the sample is moved into the reagent
film 7 positioned in the analytical section 3, where a reaction
with the reagent takes place. Then, the device is set in a
predetermined position in an electrochemical measuring apparatus,
and after a reaction of a predetermined time period, a certain
amount of voltage is applied between the working electrode and the
counter electrode, and the flowing electric current is
measured.
EXAMPLE 16
[0196] Next, an embodiment of the present invention in which a
device of the present invention is used in an analysis using
immunoassay will be described.
[0197] FIG. 21(A) shows a plan view of a device for analyzing a
sample for immunoassay. As shown in the drawing, in this device, a
liquid pooling portion 9a is formed as a depressed cylindrical
shaped cavity, and a circular opening 4a is formed thereon.
Furthermore, four analytical sections 3a, 3b, 3c, and 3d are formed
in certain positions in the drawing channel 2. A reagent film 7a
containing an antibody, which is labelled by a colored material
such as gold colloid through reaction with a target antigen in a
sample (a labelled antibody), is disposed in the analytical section
3a. Furthermore, a reagent film 7b, where an antibody which reacts
with the same antigen mentioned above is immobilized, is disposed
in the analytical section 3b. Furthermore, a rinsing solution 16 is
disposed in the analytical section 3d. The rest of the structure is
the same as in the device shown in FIG. 9 in Example 7, therefore
the same parts are referred to by using the same signs.
[0198] Immunoassay using this device is performed, for example, as
shown in FIG. 21(B)-(H). First, the suction pressure generating
chamber 1 is compressed by pressing, and in this state, the opening
4a is contacted with a sample, whereby the sample is drawn by
capillarity into the liquid pooling portion 9a to be retained (FIG.
21(B)). At this time, the rinsing solution 16 is forced to move
into the analytical section 3b by the air discharged from the
suction pressure generating chamber. Then, the pressing force
applied to the suction pressure generating chamber 1 is slightly
weakened to develop a weak suction pressure, thereby the sample is
moved into the analytical section 3a, where a reaction between the
antigen in the sample and the labelled antibody takes place (FIG.
21 (C)). At this time, the rinsing solution is moved into the
analytical section 3c by the suction pressure. Then, when the
pressure applied to the suction pressure generating chamber 1 is
completely released to develop a suction pressure, the sample is
moved into the analytical section 3b, where the antigen in the
sample is reacted with the immobilized antibody (FIG. 21(D)).
Furthermore, at this time, the rinsing solution 16 is moved into
the analytical section 3d. Then, the suction pressure generating
chamber 1 is lightly compressed again, and the resulting discharged
air forces the sample to move into the analytical section 3a (FIG.
21(E)). Then, the antigens linked to the immobilized antibodies
remain in the analytical-section 3b, the antigen being labelled by
the labelled antibodies. However, a number of labelled antibodies
which are not linked to the antigens also remain in the analytical
section 3b. At this time, the rinsing solution 16 is transferred
into the analytical section 3c. Then, the suction pressure
generating chamber 1 is further strongly compressed so that the
sample is moved into the liquid pooling portion 9a forced by the
discharged air, and also the rinsing solution 16 is moved into the
analytical section 3b (FIG. 21(F)). Then, the pressure applied to
the suction pressure generating chamber 1 is slightly released to
generate a weak suction pressure, whereby the rinsing solution 16
is moved to the analytical section 3c (FIG. 21(G)). As a result,
the analytical section 3b is rinsed, and only the antigens linked
both to the immobilized antibodies and to the labelled antibodies
are present in the analytical section 3b. At this time, the sample
is transferred into the analytical section 3a. Then, in this state,
the amount of the labelled antibodies present in the analytical
section 3c is measured by using an optical means. After measuring,
the pressure applied to the suction pressure generating chamber 1
is completely released (FIG. 21 (H)), and the device is
discarded.
[0199] Finally, it is to be understood that the invention may be
embodied in other specific forms without departing from the spirit
or essential characteristics thereof. The embodiments disclosed in
this application are to be considered in all respects as
illustrative and not restrictive, so that the scope of the
invention being indicated by the appended claims rather than by the
foregoing description, and all changes which come within the
meaning and range of equivalency of the claims are intended to be
embraced therein.
* * * * *