JP2019120557A - Assay device - Google Patents

Abstract

To provide an assay device having a simple structure, capable of simply performing an operation and improving the accuracy of concentration determination.SOLUTION: An assay device capable of determining the concentration of a sample in a liquid L comprises: inflow ports 1 and 41; inlet side flow passages 2 and 42 extended therefrom; a plurality of weighing sections 3-6 and 43-49 for storing the liquid L; a plurality of weighing flow passages 7-10 and 50-56 branched from the inlet side flow passage and connected with the plurality of weighing sections, respectively; a plurality of weighing air passages 11-14 and 57-63 connected with the plurality of weighing sections, respectively; a plurality of determination porous media 15-18 and 64-70 arranged in the plurality of weighing flow passages, respectively. The volumes W1-W4 and W11-W17 of a plurality of combination bodies obtained by combining the plurality of weighing sections with the plurality of weighing flow passages connected therewith are different from each other, and each determination porous media changes color corresponding to a sample amount in the liquid L to be passed.SELECTED DRAWING: Figure 2

Description

  The present invention relates to an assay device configured to be able to determine the concentration of an analyte in a liquid.

  In the fields of biology, chemistry, etc., examinations, experiments, assays etc. using μl (microliter) order, that is, about 1 μl or more and less than about 1 ml (milliliter) of a small amount of reagent, liquid such as treatment agent If so, a microfluidic system is utilized. The microfluidic system is configured to cause a chemical or biochemical reaction to enable detection or measurement of an analyte using a fluid. For example, in a microfluidic system, a small amount of liquid in the order of μl Biological or chemical screening is performed using

  In general, a microfluidic system includes an assay device, and conventional assay devices have been produced by film formation and the like using an expensive semiconductor manufacturing device. Such an assay device requires an external mechanism such as a pump to move the liquid, and the operation of the assay device is complicated. In addition, the durability of the assay device tends to be lowered accompanying the use of an external mechanism such as a pump, a mechanism requiring complicated operation and the like. As such, it has been desirable to improve the cost, control performance, and durability of microfluidic system assay devices.

  Therefore, in recent years, simplified assay devices such as lateral flow assay devices and flow-through assay devices have been used to improve cost, control performance, and durability. In particular, the lateral flow type assay device is simply configured to move, manipulate, etc. a liquid utilizing capillary action or the like. The simplified assay device is manufactured using a hydrophilic porous medium such as paper. Such an assay device can be manufactured at low cost, does not require an external mechanism such as a pump, and does not require a complicated operation, and thus the durability can be improved.

  Recently, in most of POCT (PointOfCareTesting), immunochromatography has been used in view of many utilities such as specificity, simplicity, low manufacturing cost, short analysis time, etc. It is also strongly desired to further increase the sensitivity of the test using the immunochromatography method. Therefore, a simple assay device is frequently used when detecting or quantifying the concentration of a sample such as an antibody or an antigen in a sample by such an immunochromatography method. In particular, a simple assay device using a hydrophilic porous medium or the like such as paper is a colorimetric assay, a fluorescence method, a light emission method, etc. which determines a color change in a test medium such as a colorimetric paper or a test agent It is used for the detection of the light intensity by

  As an example of the simplified assay apparatus, a sample attachment portion formed in a circular shape, eight channels extending radially from the sample attachment portion, and tips of these eight channels are respectively provided. And eight reaction spots each having the same length, and the sample spotting portion, each channel, and each reaction spot are formed on the paper substrate, and eight reaction spots are formed. An assay device may be coated with different color changeable reagents. In such an assay device, when a liquid such as a sample liquid containing a sample is dropped onto the sample application portion, the dropped liquid reaches each reaction spot through each flow path, and the reached liquid reaches each reaction spot. Reacts with the reagent and the reagent discolors. (See, for example, Patent Document 1)

  Another example of a simplified assay device includes a sensing area defined by a hydrophobic barrier formed on a paper substrate, a sampling area, and a microchannel, the sensing area and the sampling area being An assay device can be mentioned, which is linked by microchannels and in which at least one lanthanide ion is immobilized in the sensing area. In such an assay device, a sample containing transferrin family protein is supplied to the sampling area, and the capillary force resulting from the micropore structure of the paper substrate causes the sample to flow from the sampling area to the sensing area, When the sample comes in contact with the sensing area, a color change (a change in absorbance, reflection, etc. of the paper substrate), a change in fluorescence emission intensity, etc. occur in the detection area. By using a determination device capable of reading a signal obtained based on the intensity or the like, a color change in the sensing area, a change in fluorescence emission intensity or the like is detected. (See, for example, Patent Document 2)

International Publication No. 2012/160857 JP-A-2015-052584

  In one example related to the above-mentioned simple type assay device, eight reaction spots are each coated with different color changeable reagents, and eight reaction spots determine different reactions according to different reagents. It is only In particular, since the lengths of the eight channels are the same, the amount of liquid reaching the eight reaction spots is also the same. Therefore, even if eight reaction spots are coated with the same color-changeable reagent, the eight reaction spots can not be used to determine the concentration of the analyte in the liquid.

  In the colorimetric analysis, a semi-quantitative determination is performed in which a person determines the contrast, change, and the like of a color in a test medium that has developed or discolored while comparing it with a color sample or the like. While such colorimetric analysis can be performed at low cost and the determination process is simple, the accuracy of concentration determination is not excellent. In particular, when the concentration of the sample in the liquid is low, the difference in the color change of the test medium caused by the liquid is small, which makes the concentration determination difficult. On the other hand, in another example of the simple assay device, the determination device is used to determine the color change of the sensing area, the change of the fluorescence emission intensity, etc. However, such a determination device is expensive, And the process of the determination using the said determination apparatus becomes complicated. Therefore, in the assay device, it is desirable to facilitate its operation and improve the accuracy of concentration determination. In particular, it is desirable to improve the accuracy of concentration determination by humans.

  Considering the above situation, an assay device that can simplify the operation, improve the accuracy of the concentration determination, and improve the control performance of the liquid is desired.

  In order to solve the above problems, an assay device according to one embodiment is an assay device configured to be able to determine the concentration of an analyte in a fluid, wherein the fluid inlet is configured to flow the fluid; An inlet side channel extending from the inlet, a plurality of metering sections configured to be capable of containing the liquid, and a plurality of metrics respectively branched from the inlet side channel and connected to the plurality of metering sections A plurality of flow paths, a plurality of metering ventilation paths connected to the plurality of metering compartments so as to be hydrophobic and allow air to pass therethrough, and a plurality of determinations respectively disposed in the plurality of metering flow paths The volume of a plurality of combinations comprising different porous media and the plurality of metering channels respectively connected to the plurality of metering sections are different from each other, and each judging porous media passes through it Said liquid Configured to change its color depending on the amount of analyte in.

  In the assay device according to one embodiment, the operation can be simplified, the accuracy of concentration determination can be improved, and the control performance of the liquid can be improved.

FIG. 1 is an exploded perspective view schematically showing an assay device according to the first embodiment. FIG. 2 is a plan view schematically showing an assay device according to the first embodiment. FIG. 3 is a cross-sectional view taken along the line AA of FIG. FIG. 4 is a plan view showing the measurement section, the measurement flow path, and the porous medium for determination in order to explain the setting of the concentration rate of the porous medium for determination according to the present embodiment. FIG. 5 shows, as an example, the case where the first to fourth porous media for determination are concentrated 40 times, 20 times, 13 times, and 10 times, respectively, the sample concentration and the color change of each porous media for determination FIG. 6 (a) to 6 (c) are plan views schematically showing the flow process of a series of liquids in the assay device according to the first embodiment. FIG. 7 is a plan view schematically showing an assay device according to the second embodiment. FIG. 8 is an exploded perspective view schematically showing an assay device according to the third embodiment. FIG. 9 is a plan view schematically showing an assay device according to the third embodiment. FIG. 10 is an exploded perspective view schematically showing a porous medium for determination of the assay device according to the third embodiment and the periphery thereof. FIG. 11 is a plan view schematically showing the flow process of a series of liquids in the assay device according to the third embodiment. FIG. 12 is a plan view schematically showing the flow process of a series of liquids in the assay device according to the third embodiment, following FIG. FIG. 13 is a plan view schematically showing a flow process of a series of liquids in the assay device according to the third embodiment, following FIG. 12.

  An assay device according to the first to third embodiments of the present invention will be described. The assay device according to the present embodiment is configured to perform an assay using a liquid, and can determine the concentration of a sample in the liquid (hereinafter, referred to as “sample concentration”). The assay device of the present invention is capable of detecting the signal intensity, pattern, etc. involved in the color change reaction, optical reaction, etc. without using an analysis device etc. The color change reaction also includes color change due to concentration of the colored substance. The liquid applicable to the assay device in the present embodiment is not particularly limited as long as it can flow in the assay device. Such a liquid may typically be a water solvent, that is, an aqueous solution, and may be, for example, a body fluid such as urine, plasma, or saliva. The assay device according to the present embodiment is preferably disposable but is not limited to this, and the assay device may be reusable depending on its use mode. In FIGS. 2, 4, 6 (a) to 6 (c), 7, 9, and 11 to 13, the outline of the assay device is indicated by a broken line.

  As used herein, "lateral flow" refers to the flow of fluid that is moved by gravity settling becoming a driving force. The movement of the fluid based on the lateral flow refers to the movement of the fluid in which the driving force of the fluid by gravity sedimentation is dominant (dominated). On the other hand, the movement of fluid based on capillary force (capillary action) refers to the movement of fluid in which interfacial tension is dominant (dominated). Movement of fluid based on lateral flow and movement of fluid based on capillary force are different.

  As used herein, “microchannel” refers to the liquid in the assay device to determine the sample concentration of a trace amount of liquid on the order of μl (microliter), ie, about 1 μl or more and less than about 1 ml (milliliter). Refers to a channel configured to flow. In particular, the volume of such "microchannels" may be, but is not limited to, about 1 μl or more and less than about 1 ml.

  As used herein, “film” refers to a film-like object having a thickness of about 200 μm (micrometers) or less, and “sheet” refers to a film-like object or plate-like object having a thickness greater than about 200 μm. Point to.

  As used herein, "plastic" refers to a material that has been polymerized or shaped to use a polymerizable material or polymeric material as an essential component. Plastics also include polymer alloys combining two or more polymers.

  In the specification of the present application, a "porous medium" is a member having a plurality and a large number of micropores and capable of sucking and passing a liquid, and refers to a member including paper, cellulose membrane, non-woven fabric, plastic and the like. . For example, the "porous medium" may be hydrophilic and may be paper.

First Embodiment
First, an assay device according to the first embodiment will be described.

[Basic configuration of assay device]
Referring to FIGS. 1 and 2, the basic configuration of the assay device according to this embodiment is as follows. The assay device has an inlet 1 configured to receive the liquid L and an inlet-side flow passage 2 extending from the inlet 1. The inlet channel 2 may be a microchannel. In the inlet side channel 2, the fluid L flows from the inlet 1 in the forward flow direction away from it. Hereinafter, the upstream of the forward flow direction (indicated by the arrow F) of the liquid L in such an inlet side flow path 2 is simply referred to as “upstream”, and the downstream of the same forward flow direction is simply referred to as “downstream”.

  The assay device is branched from the four metering compartments 3, 4, 5 and 6 configured to be able to accommodate the liquid L, and the inlet channel 2 and connected to the four metering compartments 3, 4, 5 and 6, respectively. And four metering channels 7, 8, 9, 10. Hereinafter, if necessary, the four measuring sections will be referred to as first, second, third and fourth measuring sections respectively, and the four measuring channels will be respectively referred to as first, second, third and fourth measuring sections. It is called a channel. Each of the measurement channels 7 to 10 may be a microchannel. The volume (hereinafter referred to as "first measuring volume") W1 of the combination consisting of the first measuring section 3 and the first measuring channel 7, and the volume of the combination consisting of the second measuring section 4 and the second measuring channel 8 (Hereinafter referred to as "the second measurement volume") W2, the volume of a combination consisting of the third measurement section 5 and the third measurement flow passage 9 (hereinafter referred to as the "third measurement volume") W3, and the fourth measurement section The volume (hereinafter referred to as the “fourth metering volume”) W4 of the combination of the sixth and fourth metering channels 10 is different from one another.

  Such an assay device has four metering air passages 11, 12, 13, 14 connected to four metering compartments 3, 4, 5, 6, respectively, to allow air to pass through. Hereinafter, if necessary, the four metering air passages will be referred to as first, second, third and fourth metering air passages, respectively. One end portions in the longitudinal direction of the first to fourth measurement air passages 11, 12, 13, 14 are connected with the first to fourth measurement sections 3, 4, 5, 6, respectively, at connection portions 11a, 12a, 13a, 14a. It has become. The other end portions in the longitudinal direction of the first to fourth measurement air passages 11, 12, 13, 14 are open portions 11b, 12b, 13b, 14b opened toward the outside of the assay device. Each metering vent 11-14 is hydrophobic and is configured to allow air to pass but not liquid. In particular, it is preferable that the connection portions 11a to 14a of the respective measurement air passages 11 to 14 have hydrophobicity. Each metering vent 11-14 may also be a microchannel.

  The assay device further comprises four determination porous media 15, 16, 17, 18 arranged in four metering channels 7, 8, 9, 10 respectively. Hereinafter, the four determination porous media will be referred to as first, second, third, and fourth determination porous media, respectively, as necessary. Each of the judgment porous media 15 to 18 is configured to be capable of concentrating the liquid L passing therethrough, and configured to change its color according to the amount of analyte in the liquid L passing therethrough There is. Here, the liquid that “passes” the porous medium for determination refers to the liquid that flows into the porous medium for determination, and is a liquid that flows over the porous medium and flows into the measuring section and that remains in the porous medium. We say sum total of. Each porous medium for determination is to change its color according to the porous medium configured to be able to concentrate the liquid L passing therethrough and the amount of the analyte in the liquid L passing through it. It can also be composed of a porous medium which is configured.

  However, the assay device is not limited to the illustrated embodiment, and has a plurality of metering compartments and a plurality of metering channels branched from the inlet channel and connected to the plurality of metering compartments, respectively. do it. In addition, the assay device has a plurality of metering vents, each connected to a plurality of metering compartments so as to allow air to pass through, and a plurality of determining porous media, each arranged in a plurality of metering channels. be able to. The plurality is not particularly limited, but may be 2, 3, 4, 5, 6, 7, or 8 or more.

  Furthermore, the assay device includes a drawing section 19 configured to be capable of containing the liquid L, a drawing flow path 20 connecting the inlet side flow path 2 and the drawing area 19, and a drawing porous medium disposed in the drawing area 19. And 21. In such an assay device, when the liquid L reaches the drawing porous medium 21, the drawing porous medium 21 causes the liquid L to be drawn from the drawing channel 20 into the drawing section 19.

[Specific configuration of assay device]
The specific configuration of the assay device according to the present embodiment is as follows. As shown in FIGS. 1 and 2, the first to fourth measurement channels 7 to 10 branch from the inlet channel 2 sequentially in the forward flow direction. The four measurement channels 7 to 10 branch from the four measurement branches 2a, 2b, 2c and 2d of the inlet channel 2, respectively. Hereinafter, if necessary, the four metering branches will be referred to as first, second, third and fourth metering branches, respectively. The first to fourth measurement branch portions 2 a to 2 d are sequentially arranged in the forward flow direction in a state in which the first to fourth measurement branch portions 2 a to 2 d are spaced from each other in the longitudinal direction of the inlet side flow path 2. Further, the downstream end 2 e of the inlet side flow passage 2 and the upstream end 20 a of the lead-in flow passage 20 are connected.

  In such an assay device, four metering compartments 3-6 may be sequentially filled with liquid L in the forward flow direction, and the four metering channels 7-10 may also be filled with liquid L sequentially in the forward flow direction. Good to be done. Furthermore, each weighing section 3 to 6 of the assay device, weighing branch parts 2a to 2d corresponding to the weighing sections 3 to 6, weighing channels 7 to 10 corresponding to the weighing sections 3 to 6, and the weighing sections 3 to 6 For the flow of the liquid L associated with the measuring air passages 11 to 14 corresponding to the and the judgment porous media 15 to 18 corresponding to the measuring areas 3 to 6, typically, the measuring areas 3 to 6 and the measured flow Before the channels 7 to 10 are filled with the liquid L, the control of the liquid L based on the capillary force of the judgment porous medium 15 to 18 causes the inlet side channel 2 to pass through the metering channels 7 to 10 and the metering section It is preferable that the amount of the liquid L flowing into 3 to 6 be larger than the amount of the liquid L flowing from the metering branch portions 2 a to 2 d to the downstream of the inlet side flow path 2. At this time, the amount of air flowing from the measuring sections 3 to 6 to the measuring air passages 11 to 14 may also be larger than the amount of air flowing from the measuring branches 2 a to 2 d in the forward flow direction of the inlet side flow passage 2. Such a flow of the liquid L is obtained by adjusting the capillary force of the judgment porous medium 15 to 18, the inlet side flow passage 2, the measurement flow passages 7 to 10, the cross sectional area of the measurement air passages 11 to 14, etc. be able to. The present invention is not limited to this, and in the assay device, the measuring section is adjusted by adjusting the capillary force of the porous medium for determination, the inlet side channel, the measuring channel, the cross sectional area of the measuring air passage, etc. The amount of liquid flowing in may be smaller than the amount of liquid flowing from the metering branch in the forward flow direction of the inlet channel. Furthermore, the amount of air flowing from the measuring section to the measuring air passage may be smaller than the amount of air flowing from the metering branch in the forward flow direction of the inlet channel.

  As shown in FIG. 1, the assay device has top and bottom surfaces facing each other. The direction extending between the top and bottom surfaces of the assay device is defined as the thickness direction. Such an assay device has a first layer member S1, a second layer member S2, and a third layer member S3 arranged in order from the top surface to the bottom surface. The first to third layer members S1 to S3 are formed substantially in layers.

  The assay device has a laminated structure in which such first to third layer members S1 to S3 are laminated. The contact angles of the first to third layer members S1 to S3 may be smaller than 90 degrees. The material of each of the first to third layer members S1 to S3 may be the same or different, and may be a plastic sheet or film.

  As shown in FIG. 1, the inlet 1 is formed to penetrate the first layer member S1 in the thickness direction. The inlet-side flow passage 2, the four measurement sections 3 to 6, the four measurement flow paths 7 to 10, the four measurement air flow paths 11 to 14, the drawing in section 19, and the drawing in flow path 20 The layer member S2 is formed to penetrate in the thickness direction. Further, the inlet side flow passage 2, the four measurement flow passages 7 to 10, and the four measurement air flow passages 11 to 14 are formed to extend along the planar direction of the second layer member S1. The top surface and the bottom surface of each of the inlet-side channel 2, the four metering sections 3 to 6, the four metering channels 7 to 10, the lead-in section 19 and the lead-in channel 20 are respectively the first and third layer members It is defined by S1 and S3.

  Referring to FIGS. 1 to 3, the top and bottom surfaces of the four metering air passages 11 to 14 except for the connecting portions 11 a to 14 a are respectively defined by the first and third layer members S 1 and S 3. The top and bottom surfaces of the connection portions 11a to 14a in each of the metering air passages 11 to 14 are defined by the top and bottom adhesive tapes T1 and T2, respectively. The adhesive G of the adhesive tapes T1 and T2 is positioned on the top and bottom surfaces of the connection portions 11a to 14a. By this, the connection parts 11a-14a of each measurement ventilation path 11-14 have hydrophobicity. Adhesive G can be selected to have a contact angle greater than 90 degrees. In particular, it is more preferable that the three surfaces of the connection portions 11a to 14a of the measuring air passages 11 to 14 be hydrophobic. Air can pass through each connection 11a-14a, but the liquid L can not substantially pass through each connection 11a-14a. Alternatively, the measuring air passages 11 to 14 may be made hydrophobic by providing a layer of a hydrophobic substance other than the adhesive on at least one of the top surface and the bottom surface of the connection portion.

  As shown in FIG. 2, the inlet 1 is disposed corresponding to the upstream end 2 f of the inlet-side flow passage 2. The inlet side flow passage 2 may extend substantially linearly. The width of the upstream end 2 f of the inlet-side flow passage 2 may be wider than the width of the other portion of the inlet-side flow passage 2. Furthermore, the inlet channel 20 may also extend substantially linearly, and in particular, the inlet channel 2 and the inlet channel 20 may extend continuously and generally linearly.

  Each of the measurement sections 3 to 6 is disposed on one side in the width direction of the inlet side flow path 2 with respect to the inlet side flow path 2. Each of the measurement sections 3, 4, 5, 6 has an inner end located closer to the inlet channel 2 in the width direction of the inlet channel 2, and an inner end in the width direction of the inlet channel 2. And having opposite outer ends. Each of the metering sections 3 to 6 extends substantially linearly in the direction intersecting the longitudinal direction of the inlet side flow passage 2. In particular, each of the measurement sections 3 to 6 may extend substantially linearly in the direction substantially orthogonal to the longitudinal direction of the inlet side flow passage 2. In another embodiment not shown, a part of the plurality of measurement sections is disposed on one side in the width direction of the inlet side channel, and another part of them is in the width direction of the inlet side channel It may be disposed on the other side.

  The first to fourth measurement volumes W1 to W4 decrease successively in the forward flow direction. In this case, the sum of the lengths of the first measuring section 3 and the first measuring channel 7 (hereinafter referred to as “first concentrated length”) D1 and the lengths of the second measuring section 4 and the second measuring channel 8 (Hereinafter referred to as "second concentration length") D2, the sum of the lengths of third measuring section 5 and third measurement channel 9 (hereinafter referred to as "third concentration length") D3, and The sum of the lengths of the fourth measuring section 6 and the fourth measuring channel 10 (hereinafter referred to as "fourth concentrated length") D4 may be sequentially decreased in the forward flow direction, and the first to fourth measuring sections 3 to 3 The cross-sectional area of 6 and the cross-sectional areas of the first to fourth measurement channels 7 to 10 may be substantially equal. In addition, the cross-sectional area here shall mean the cross-sectional area perpendicular | vertical to the longitudinal direction of each measurement flow paths 7-10 and the measurement divisions 3-6.

  However, the first to fourth metering volumes can also be increased sequentially from upstream to downstream. In this case, it is preferable that the first to fourth concentration lengths sequentially increase from upstream to downstream, and further, the cross-sectional areas of the first to fourth measurement sections and the cross-sectional areas of the first to fourth measurement channels It is good that

  One ends of the first to fourth measurement channels 7 to 10 in the longitudinal direction are respectively connected to the first to fourth measurement branches 2 a to 2 d of the inlet-side channel 2. The other longitudinal ends of the first to third measurement channels 7 to 10 are connected to the inner ends of the first to third measurement sections 3 to 6, respectively. Each of the metering channels 7 to 10 extends in a substantially straight line in a direction intersecting the longitudinal direction of the inlet channel 2. In particular, each of the measurement flow paths 7 to 10 may extend substantially linearly in the direction substantially orthogonal to the longitudinal direction of the inlet side flow path 2.

  The first to fourth porous media for determination 15 to 18 are configured to be able to block the passage of air in the first to fourth measurement channels 7 to 10, respectively. Furthermore, each measuring section 3 to 6 of the assay device, measuring branch parts 2a to 2d corresponding to the measuring section 3 to 6, the measuring flow path 7 to 10 corresponding to the measuring section 3 to 6, and the measuring section 3 to 6 For the flow of liquid L associated with the determination porous media 15-18 corresponding to 6, typically the capillary of the metering porous media 15-18 before the metering compartments 3-6 are filled with the liquid L. By control of the liquid L based on force, compared with the downstream side of the forward flow direction of the inlet side flow path 2 from the measurement branch portions 2a to 2d, the liquid preferentially from the measurement branch portions 2a to 2d to the measurement flow paths 7 to 10 It is possible to flow L. In this state, the flow of the liquid L from the metering branches 2a to 2d toward the downstream side in the forward flow direction of the inlet channel 2 is stopped or the metering channels 7 from the metering branches 2a to 2d. It becomes slower than the flow of the liquid L flowing to. Thereafter, when the measuring sections 3 to 6 are filled with the liquid L, the flow of the liquid L from the measuring branch sections 2a to 2d toward the downstream side in the forward flow direction of the inlet side flow path 2 is stopped as described above. Or resume from a slow state as described above.

  The widths of the first to fourth porous media for determination 15 to 18 are substantially the same as the widths of the first to fourth measurement channels 7 to 10, respectively. One end of each of the first to fourth porous media for determination 15 to 18 in the longitudinal direction may be arranged to substantially coincide with one end of each of the first to fourth measurement channels 7 to 10. When the other ends of the first to fourth porous media for determination 15 to 18 in the longitudinal direction are also arranged to substantially coincide with the other ends of the first to fourth measurement channels 7 to 10, respectively. Good. The thicknesses of the first to fourth porous media for determination 15 to 18 become substantially equal to the heights of the first to fourth measurement channels 7 to 10, that is, the thickness of the second substrate S2, respectively. Good to have. In other words, it is preferable that the first to fourth measurement channels 7 to 10 are closed by the first to fourth porous media for determination 15 to 18, respectively. It is preferable that the volumes of the measurement channels 7 to 10 and the volumes of the porous media for judgment 15 to 18 disposed in the channels be substantially equal. Further, it is preferable that the volumes of the first to fourth measurement channels 7 to 10 be substantially equal to one another, and the volumes of the first to fourth porous media for determination 15 to 18 be substantially equal to one another. However, as long as a predetermined concentration rate can be achieved by setting the concentration rate described later, the volumes of the plurality of porous media for determination may be different from each other.

  The volume W5 of the lead-in section 19 may be larger than the sum of the first to fourth measurement volumes W1 to W4. The pull-in porous medium 21 has a main body portion 21 a disposed in the pull-in section 19 and a protrusion 21 b projecting from the pull-in section 19 into the pull-in channel 20. In particular, the body portion 21 a of the porous withdrawal medium 21 may be arranged to occupy the withdrawal section 19. The projecting portion 21 b can be configured to urge the liquid L in the drawing channel 20 to be drawn into the drawing section 19.

  Furthermore, as shown in FIG. 1 and FIG. 2, the assay device comprises four transparent determination windows 22 and 23 formed in the first layer member S1 respectively corresponding to the four determination porous media 15-18. , 24, 25 may be included. Hereinafter, as necessary, the four determination windows will be referred to as first, second, third and fourth determination windows, respectively. In this case, in the first layer member S1, portions other than the first to fourth determination window portions 22 to 25 may be opaque. When the first layer member is transparent, the determination window may not be provided.

  In the production process of such an assay device, when the first to third layer members S1 to S3 are arranged to be stacked in this order, as described above, the first to fourth porous media for judgment 15 to 45 are provided. 18 and the porous porous medium 21 are arranged. Thereafter, the first and second layer members S1 and S2 are adhered to each other, and the second and third layer members S2 and S3 are adhered to each other.

[About setting of concentration rate of porous medium for judgment]
The setting of the concentration ratio of the porous media for determination 15 to 18 will be described with reference to FIGS. 4 and 5. As shown in FIG. 4, the concentration ratio of the porous media for determination 15-18 is determined based on the measurement volumes W1 to W4 corresponding to the porous media for determination 15-18. Specifically, the concentration rate is determined by multiplying the measurement volumes W1, W2, W3, and W4 with respect to the volumes V1, V2, V3, and V4 of the porous media 15 to 18 for determination W1 / V1, W2 / V2, W3 / V3, It is determined based on W4 / V4. For example, in the case where measuring sections 3 to 6, measuring channels 7 to 10, and porous media for determination 15 to 18 linearly extend with substantially equal cross-sectional areas, the concentration rate is the porous media for determination It can be determined based on the magnifications D1 / E, D2 / E, D3 / E, D4 / E of the first to fourth concentrated lengths D1, D2, D3, D4 with respect to the length E of 15-18. It should be noted that if the concentration rate is about 1 ×, the volume of the metering compartment located between the metering channel and the metering vent will be substantially zero and this metering compartment will be substantially absent. However, in the present invention, such a metering compartment is present even if the concentration factor is about 1 × and the volume of the metering compartment located between the metering channel and the metering vent is substantially zero. Defined as

  For example, as shown in FIG. 5, the concentration ratios of the first, second, third, and fourth porous media for determination 15-18 (hereinafter referred to as “first, second, third, and as necessary, When making C1, C2, C3, and C4 about the fourth concentration ratio about 40 times, about 20 times, about 13 times, and about 10 times, respectively, the following first to fourth porous media for judgment 15 It is possible to confirm the color change of ~ 18. First, when the liquid L generated at the first sample concentration B1 of about 0% is introduced into the assay device, the first to fourth determinations set to the first to fourth concentration ratios C1 to C4, respectively. The colors of the porous media 15-18 hardly change.

  Next, when the liquid L produced at a second sample concentration B2 of about 2.5% is introduced into the assay device, the color of the first judgment porous medium 15 set to the first concentration ratio C1 Change in depth. The color of the second judgment porous medium 16 set to the second concentration ratio C2 is lighter than the color of the first judgment porous medium 15. The colors of the third and fourth porous media for judgment 17 and 18 respectively set to the third and fourth concentration ratios C3 and C4 hardly change.

  When the liquid L produced at a third sample concentration B3 of about 5% is introduced into the assay device, the first and second determination porousities set to the first and second concentration ratios C1 and C2, respectively The colors of the media 15 and 16 change in almost the same manner. The color of the third judgment porous medium 17 set to the third concentration ratio C3 is lighter than the color of the second judgment porous medium 16. The color of the fourth judgment porous medium 18 set to the fourth concentration ratio C4 is lighter than the color of the third judgment porous medium 17.

  When the liquid L produced at the fourth sample concentration B4 of about 7.5% is introduced into the assay device, the first to third judgments set to the first to third concentration ratios C1 to C3 are made. The colors of the porous media 15-17 change in the same manner and intensity. The color of the fourth judgment porous medium 18 set to the fourth concentration ratio C4 is lighter than the color of the third judgment porous medium 17.

  When the liquid L produced at the fifth sample concentration B5 of about 10% is introduced into the assay device, the first to fourth porous media for judgment 15 to the first to fourth concentration ratios C1 to C4 are respectively set. The 18 colors change in much the same way. In such an assay device, especially when measuring low concentration samples, compared to what was conventionally measured without concentration, by means of a metering compartment and metering channels that achieve a plurality of different enrichment ratios. It becomes possible to semi-quantify with finer precision.

[Fluid control of assay device]
The fluid control of the assay device according to the present embodiment will be described with reference to FIGS. 6 (a) to 6 (c). The first to fourth determination window portions 22 to 25 are omitted in FIGS. 6A to 6C. As shown in FIG. 6A, when the liquid L is continuously supplied to the inlet 1 in the assay device, the liquid L first flows from the inlet 1 to the inlet-side flow path 2 based on the lateral flow. The liquid L flows to the first measurement branch 2a. Next, in the first measurement branch portion 2a, before the first measurement section 3 and the first measurement flow path 7 are filled with the liquid L, as shown by the arrow p1, the liquid L is porous for the first determination The first metering branch flows from the inlet channel 2 through the first metering channel 7 into the first metering zone 3 based on the capillary force of the medium 15 and as indicated by the arrow F on the basis of the lateral flow. It flows in the forward flow direction of the inlet side flow passage 2 beyond the part 2a. At this time, typically, the amount of the liquid L flowing into the first measurement section 3 may be larger than the amount of the liquid L flowing in the forward flow direction of the inlet side flow passage 2 from the first measurement branch portion 2a, The amount of air flowing from the first measurement section 3 to the first measurement air passage 11 may also be larger than the amount of air flowing in the forward flow direction of the inlet side passage 2 from the first measurement branch 2a. However, the present invention is not limited to this, and in the assay device, the amount of liquid flowing into the first measuring section is smaller than the amount of liquid flowing from the first measuring branch in the forward flow direction of the inlet channel. And the amount of air flowing from the first metering section to the first metering passage may also be smaller than the amount of air flowing from the first metering branch in the forward flow direction of the inlet channel.

  In a state in which the first measurement section 3 and the first measurement flow path 7 are filled with the liquid L, the amount of the analyte contained in the liquid L of the amount corresponding to the first measurement volume W1 of the first judgment porous medium 15 Change its color according to. After the first metering section 3 and the first metering channel 7 are filled with the liquid L, all of the liquid L passing through the first metering branch 2a in the inlet channel 2 is subjected to the first metering based on the lateral flow. It flows in the forward flow direction of the inlet side flow path 2 from the branch part 2a.

  Furthermore, the liquid L flows to the second metering branch 2 b, and the second metering section 4 and the second metering flow path 8 are filled with the liquid L as in the first metering section 3. In a state in which the second measurement section 4 and the second measurement flow path 8 are filled with the liquid L, the amount of the analyte contained in the liquid L in an amount corresponding to the second measurement volume W2 of the second judgment porous medium 16 Change its color according to.

  After the second metering section 4 and the second metering channel 8 are filled with the liquid L, the liquid L flows to the third metering branch 2 c and, like the first metering section 3, the third metering section 5 and the third metering section 3. The metering channel 9 is filled with the liquid L. In a state in which the third measurement section 5 and the third measurement flow path 9 are filled with the liquid L, the amount of the analyte contained in the liquid L in an amount corresponding to the third measurement volume W3 of the third judgment porous medium 17 Change its color according to.

  After the third metering section 5 and the third metering channel 9 are filled with the liquid L, the liquid L flows to the fourth metering branch 2 d and, like the first metering section 3, the fourth metering section 6 and the fourth metering section The metering channel 10 is filled with the liquid L. In a state where the fourth measurement section 6 and the fourth measurement flow path 10 are filled with the liquid L, the amount of the analyte contained in the liquid L in an amount corresponding to the fourth measurement volume W4 of the fourth judgment porous medium 18 Change its color according to.

  As shown in FIG. 6 (b), after the first to fourth measuring sections 3 to 6 and the first to fourth measuring channels 7 to 10 are sequentially filled with the liquid L, the liquid L passes through the drawing-in path 20. When reaching the inlet porous medium 21, the liquid L remaining in the inlet channel 2 and the inlet passage 20 is drawn into the inlet section 19 based on the capillary force of the inlet porous medium 21 (hereinafter required) In response to this, the "retraction action" is initiated. Furthermore, after the first to fourth measuring sections 3 to 6 and the first to fourth measuring channels 7 to 10 are sequentially filled with the liquid L, the inflow port is called at a predetermined timing (hereinafter referred to as "supply stop timing") When the supply of the liquid L to 1 is stopped, air is sent from the inlet 1 to the inlet side path 2 and the inlet path 20.

  In this case, as shown in FIG. 6C, the inlet porous medium 21 draws in the liquid L remaining in the inlet side flow passage 2 and the inlet passage 20. Then, the liquid L in which the porous media for drawing 21 remains is held in the drawing section 19, and the liquid L filled in each of the first to fourth measuring sections 3 to 6 as described above is the first. The liquid L held by the fourth porous medium for determination 15 to 18 as it is and filled in each of the first to fourth measurement channels 7 to 10 is also a porous medium for first to fourth determination, respectively. It is kept as it is by 15-18. As a result, it is possible to measure the liquid L to a desired amount corresponding to each of the measurement volumes W1 to W4, and it is possible to accurately determine the concentration of the sample in the liquid L by the respective determination porous media 15 to 18. In addition, as for the said supply stop timing, the liquid L with which the 1st-4th measurement divisions 3-6 and the 1st-4th measurement flow paths 7-10 were filled is hold | maintained as it is, and the inlet side flow path 2 and a drawing-in path It can be defined that the liquid L remaining at 20 is accommodated in the drawing section 19.

[About concentration determination of assay device]
The concentration determination of the assay device according to the present embodiment will be described with reference to FIG. In the state where all of the first to fourth measuring sections 3 to 6 and the first to fourth measuring channels 7 to 10 are filled with the liquid L because the first to fourth measuring volumes W1 to W4 are different. The degree of color change of the first to fourth porous media for determination 15 to 18 differs depending on the first to fourth measurement volumes W1 to W4 and the concentration of the sample in the liquid L, respectively. More specifically, the hue, saturation, lightness, or luminance of the first to fourth porous media for determination 15 to 18 respectively indicate the first to fourth measurement volumes W1 to W4 and the specimens in the liquid L. Depending on the concentration of For example, when the first to fourth measuring volumes W1 to W4 decrease sequentially from the upstream to the downstream, all of the first to fourth measuring sections 3 to 6 and the first to fourth measuring channels 7 to 10 are In the state of being filled with the liquid L, the degree of color change of the first to fourth porous media for determination 15 to 18 sequentially decreases.

  As described above, the assay device according to the present embodiment has, in its basic configuration, the inflow port 1 configured to flow the liquid L, the inlet-side flow path 2 extending from the inflow port 1, and the liquid L A plurality of metering compartments 3 to 6 which can be configured, and a plurality of metering channels 7 to 10 respectively branched from the inlet channel 2 and connected to the plurality of metering compartments 3 A plurality of metering vents 11 to 14 connected to the plurality of metering compartments 3 to 6 respectively and arranged to be able to pass air, and arranged on the plurality of metering channels 7 to 10 respectively A plurality of determination porous media 15 to 18 are provided, the plurality of measurement volumes W 1 to W 4 are different from each other, and each determination porous media 15 to 18 is in accordance with the amount of the specimen in the liquid L passing through it. The color is changed.

  Therefore, as described in the fluid control and concentration determination of the assay device described above, in the assay device in which a plurality of measurement volumes W1 to W4 are defined according to the desired amount of liquid L, the liquid L is continuously applied to the inlet 1 The liquid L can be accurately measured in the desired amount corresponding to each of the measurement volumes W1 to W4. As a result, in each of the metering zones 3 to 6 and the corresponding metering channels 7 to 11 it is possible to concentrate at the desired exact magnification. And since the degree of color change of the plurality of porous media for judgment 15 to 18 changes according to the liquid L accurately measured in this manner, the color change degree is compared with the color change pattern etc. The sample concentration can be accurately determined without using a device that analyzes the signal of. Therefore, the operation of the assay device can be simplified, the accuracy of the concentration determination can be improved, and the control performance of the liquid can be improved. In particular, it is possible to greatly improve the accuracy of semi-quantitative determination in a liquid containing a small amount of sample, which has hitherto been substantially impossible to distinguish visually.

  The assay device according to the present embodiment has, in its basic configuration, a drawing section 19 configured to be capable of containing the liquid L, a drawing channel 20 connecting the inlet side channel 2 and the drawing section 19, and a drawing section And 19 a porous media 21 for drawing. Then, the liquid L can be drawn into the drawing section 19 from the drawing channel 20 by the drawing porous medium 21 in a state where the liquid L reaches the drawing porous medium 21. Therefore, as described in the fluid control of the assay device described above, since the liquid L remaining in the inlet side flow path 2 and the suction path 20 can be reliably recovered in the suction section 19, the control performance of the liquid L is improved. It can be improved.

  According to the assay device of the present embodiment, in the specific configuration, the downstream end 2e of the inlet channel 2 and the upstream end 20a of the inlet channel 20 are connected, and a plurality of meterings are performed. The channels 7 to 10 branch from the inlet channel 2 sequentially in the forward flow direction of the inlet channel 2. The plurality of measuring sections 3 to 6 and the measuring channels 7 to 10 can be sequentially filled with the liquid L in the forward flow direction of the inlet side channel 2. Furthermore, in each of the measuring sections 3 to 6, the measuring branch portions 2a to 2d corresponding to the measuring sections 3 to 6, the measuring flow paths 7 to 10 corresponding to the measuring sections 3 to 6, and the measuring sections 3 to 6 respectively For the corresponding determination porous media 15-18, typically, the capillary force of the determination porous media 15-18 is applied before the metering compartments 3-6 and the metering channels 7-10 are filled with the liquid L. The amount of the liquid L flowing from the inlet side channel 2 through the measuring channels 7 to 10 into the measuring sections 3 to 6 is controlled by the control of the liquid L based on the downstream of the inlet side channel 2 from the measuring branches 2a to 2d. Should be larger than the amount of liquid L flowing to the Therefore, as described in the fluid control of the above-mentioned assay device, if the liquid L is continuously supplied to the inflow port 1, the liquid L can be metered into each of the metering sections 3-6 and the metering channels 7-10. In addition, the desired quantity corresponding to each of the measurement volumes W1 to W4 can be accurately measured. Therefore, the operation of the assay device can be simplified, the accuracy of the concentration determination can be improved, and the control performance of the liquid can be improved.

Second Embodiment
An assay device according to the second embodiment will be described. The assay device according to the present embodiment is the same as the assay device according to the first embodiment except for the points described below. Therefore, in the present embodiment, the description of the same configuration as that of the assay device according to the first embodiment is omitted.

[About the configuration of the assay device]
The configuration of the assay device according to the present embodiment is as follows. As shown in FIG. 7, the assay device according to the present embodiment has an inflow porous medium 31 disposed at the upstream end 2 f of the inlet side flow channel 2 corresponding to the inlet 1. The inflow porous medium 31 may be arranged to occupy one end 2 d of the inlet side flow path 2. The assay device also has an inlet side branched from the vent branch portion 2g of the inlet side flow path 2 located between the inlet 1 and the first measurement branch portion 2a closest to the inlet 1 so as to allow air to pass therethrough. It has an air passage 32.

  More specifically, one end of the inlet-side air passage 32 in the longitudinal direction is a connection portion 32 a connected to the air-flow branching portion 2 g of the inlet-side flow passage 2. The other end in the longitudinal direction of the inlet side air passage 32 is an open portion 32 b that opens toward the outside of the assay device. The inlet side air passage 32 is hydrophobic. In particular, the connecting portion 32a of the inlet side air passage 32 may be hydrophobic. The inlet side air passage 32 may also be a microchannel. The inlet side air passage 32 extends in a substantially straight line in a direction intersecting the longitudinal direction of the lead-in passage 20. In particular, the inlet side air passage 32 may extend substantially linearly in the direction substantially orthogonal to the longitudinal direction of the lead-in flow passage 20.

  Although not shown in particular clearly, the inlet side air passage 32 is formed to penetrate the second layer member S2 in the thickness direction. The inlet side air passage 32 is also formed to extend along the planar direction of the second layer member S1. The top and bottom surfaces of portions of the inlet side air passage 32 other than the connecting portion 32a are respectively defined by the first and third layer members S1 and S3. The connection portion 32a in the inlet side air passage 32 is made hydrophobic by the adhesive tapes T1 and T2 as in the case of the respective measurement air passages 11-14.

[Fluid control of assay device]
The fluid control of the assay device according to the present embodiment is the same as the fluid control of the assay device according to the first embodiment except for the points described below. Therefore, in the present embodiment, description of the same points as the fluid control of the assay device according to the first embodiment will be omitted.

  In the assay device according to the present embodiment, when the liquid L is continuously supplied to the inflow port 1, the liquid L is first subjected to the inflow porous medium from the inflow port 1 by the capillary force of the inflow porous medium 31. It is urged to move towards the inlet channel 2 through 31. Thereafter, the liquid L flows from the inflowing porous medium 31 to the first metering branch 2a based on the lateral flow. In addition, after the first to fourth measuring sections 3 to 6 and the first to fourth measuring channels 7 to 10 are sequentially filled with the liquid L, the supply stop timing to the inflow port 1 is the same as the first embodiment. When the supply of the liquid L is stopped, air may be sent from the inlet side air passage 32 to the inlet side flow passage 2 and the inlet flow passage 20. In the state where the supply of the liquid L is stopped, the air does not flow in a part of the drawing-in flow path 2 located between the inflow porous medium 31 and the inlet side air passage 32, so the liquid L remains. In addition, when the supply of the liquid L is stopped, the inflowing porous medium 31 is typically substantially free of the liquid L or in a state of being wetted by the liquid L.

  As mentioned above, in addition to the effect similar to the said 1st Embodiment, in the assay apparatus which concerns on this embodiment, the following effect can be acquired. The assay device according to the present embodiment includes an inflow porous medium 31 disposed corresponding to the inflow port 1, a hydrophobic property, and the inflow port 1 and a first measurement branch closest to the inflow port 1. It further comprises an inlet side air passage 32 branched from the air flow branch portion 2g located between 2a. Therefore, the flow of the liquid L in the forward flow direction can be reliably generated in the inlet side flow path 2 by the capillary force of the inflow porous medium 31. In addition, after the first to fourth measurement sections 3 to 6 and the first to fourth measurement channels 7 to 10 are sequentially filled with the liquid L, the inlet channel 2 and the inlet channel 2 from the inlet air channel 32 The air delivered to 20 can ensure that the liquid L is drawn from the inlet channel 20 into the inlet compartment 19. Therefore, the control performance of the liquid L can be improved.

Third Embodiment
An assay device according to a third embodiment will be described.

[Basic configuration of assay device]
Referring to FIG. 8 and FIG. 9, the basic configuration of the assay device according to this embodiment is as follows. The assay device has an inlet 41 configured to flow the liquid L, and an inlet-side flow passage 42 extending from the inlet 41. The inlet side channel 42 may be a microchannel. In the inlet side channel 42, the fluid L flows from the inlet 41 in the forward flow direction away from it. Hereinafter, the upstream of the forward flow direction (indicated by the arrow F) of the liquid L in such an inlet side flow channel 42 is simply referred to as “upstream”, and the downstream of the same forward flow direction is simply referred to as “downstream”.

  The assay device comprises seven measuring sections 43, 44, 45, 46, 47, 48, 49 configured to be capable of containing liquid L, and a branch from the inlet side flow channel 42, and seven measuring sections 43, 44, There are seven metering channels 50, 51, 52, 53, 54, 55, 56 connected to 45, 46, 47, 48, 49 respectively. Hereinafter, as necessary, seven measurement sections will be referred to as first, second, third, fourth, fifth, sixth and seventh measurement sections, respectively, and seven measurement channels will be respectively referred to Called 2, 2, 3, 4, 5, 6, and 7 metering channels. Each of the measurement channels 50 to 56 may be a microchannel. In addition, a combination (hereinafter referred to as “first measurement volume”) W11 of a combination including the first measurement section 43 and the first measurement flow passage 50, and a combination including the second measurement distribution 44 and the second measurement flow passage 51 Volume (hereinafter referred to as “second measurement volume”) W12, volume (hereinafter referred to as “third measurement volume”) W13 of a combination including the third measurement section 45 and the third measurement flow channel 52, and The volume (hereinafter referred to as “fourth measurement volume”) W 14 of the combination including the measurement section 46 and the fourth measurement flow channel 53 and the volume (hereinafter referred to as “the combination of the fifth measurement section 47 and the fifth measurement flow channel 54 , “The fifth measuring volume” W15, the combined volume consisting of the sixth measuring section 48 and the sixth measuring channel 55 (hereinafter referred to as “the sixth measuring volume”) W16, the seventh measuring section 49 and The volume of the combination comprising the seventh metering channel 56 ( Below, they are different from each other as "seventh metering volume" that) W17.

  Furthermore, the assay device comprises seven metering vents 57, 58, 59, 60, each connected to seven metering compartments 43, 44, 45, 46, 47, 48, 49 to allow air to pass through. 61, 62, 63 are included. Hereinafter, the seven metering vents will be referred to as first, second, third, fourth, fifth, sixth and seventh metering vents, respectively, as required. One ends of the first to seventh measuring air passages 57, 58, 59, 60, 61, 62, 63 in the longitudinal direction respectively correspond to the first to seventh measuring sections 43, 44, 45, 46, 47, 48, The connection portions 57a, 58a, 59a, 60a, 61a, 62a, 63a with the 49 are provided. The other longitudinal ends of the first to seventh measuring air passages 57, 58, 59, 60, 61, 62, 63 are open parts 57b, 58b, 59b, 60b, 61b which open toward the outside of the assay device. , 62b, 63b. Each metering vent 57-63 is hydrophobic and is configured to allow air to pass but not liquid. In particular, it is preferable that the connection portions 57a to 63a of the respective measurement air passages 57 to 63 have hydrophobicity. Each metering vent channel 57-63 may also be a microchannel.

  The assay device further comprises seven determination porous media 64, 65, 66, 67, 68, 69, 70 arranged in seven metering channels 50, 51, 52, 53, 54, 55, 56 respectively. . Hereinafter, the seven determination porous media will be referred to as first, second, third, fourth, fifth, sixth, and seventh determination porous media, respectively, as necessary. Each of the judgment porous media 64 to 70 is configured to be able to concentrate the liquid L passing therethrough, and to change its color in accordance with the amount of analyte in the liquid L passing therethrough There is. Each determination porous medium is configured to be capable of concentrating the liquid L passing therethrough, and configured to change its color according to the amount of the porous medium and the analyte in the liquid L passing therethrough. It can also be composed of a porous medium.

  However, the assay device is not limited to the illustrated embodiment, and has a plurality of metering compartments and a plurality of metering channels branched from the inlet channel and connected to the plurality of metering compartments, respectively. do it. In addition, the assay device has a plurality of metering vents, each connected to a plurality of metering compartments so as to allow air to pass through, and a plurality of determining porous media, each arranged in a plurality of metering channels. be able to. The plurality is not particularly limited, but may be 2, 3, 4, 5, 6, 7, or 8 or more. In addition, in the case where there are a plurality of measurement sections, the amount of liquid that can be accommodated and measured in the plurality of measurement sections may be the same or different.

  Furthermore, the assay device has a drawing section 71 configured to be capable of containing the liquid L, and a drawing channel 72 connecting the inlet side channel 42 and the drawing section 71. The inlet channel 72 has an upstream portion 72a and a downstream portion 72b located downstream of the upstream portion 72a. The upstream portion 72a and the downstream portion 72b are connected to each other.

  The assay device also has a porous withdrawal medium 73 disposed in the withdrawal compartment 71. In such an assay device, when the liquid L reaches the inlet porous medium 73, the liquid porous L is drawn into the inlet section 71 from the inlet channel 72 by the inlet porous medium 73.

[Specific configuration of assay device]
Referring to FIGS. 8 to 10, the specific configuration of the assay device according to this embodiment is as follows. As shown in FIG. 8, the assay device has top and bottom surfaces facing each other. The direction extending between the top and bottom surfaces of the assay device is defined as the thickness direction. The assay device has a top surface layer member M1, an inflow layer member M2, a distribution layer member M3, a determination layer member M4, a storage layer member M5, and a bottom surface layer member M6 arranged in order from the top surface to the bottom surface.

  Each of the layer members M1 to M6 is formed substantially in a layer shape. The inflow layer member M2 is located on the back side with respect to the top surface layer member M1. The distribution layer member M3 is located on the back side of the inflow layer member M2. The determination layer member M4 is located on the back side of the distribution layer member M3. The containing layer member M5 is located on the back side with respect to the determination layer member M4. The bottom layer member M6 is located on the back side of the containing layer member M5.

  The assay device has a laminated structure in which these layer members M1 to M6 are laminated. As shown in FIGS. 8 to 10, the liquid L is fed in a forward flow direction from the front surface to the rear surface of the laminated structure. The contact angles of the layer members M1 to M6 may be smaller than 90 degrees. The material of each of the layer members M1 to M6 may be the same or different, and may be a plastic sheet or film.

  As shown in FIGS. 8 and 9, in such an assay device, the inlet channel 42 has a main body 42 a extending from the inlet 41. The inlet-side flow passage 42 connects the main body portion 42a to the first to seventh measurement flow passages 50, 51, 52, 53, 54, 55, 56 respectively to form first to seventh measurement connection portions 42b, 42c, 42d, 42e, 42f, 42g, 42h. The inlet side flow passage 42 also has a pull-in connection portion 42i that makes the main body portion 42a communicate with the pull-in flow passage 72. Furthermore, the inlet-side flow passage 42 is a porous media for distribution configured to be able to suction so as to distribute the liquid L sent from the inlet 41 to the first to seventh measuring connections 42b to 42h and the pulling connection 42i. And 42j.

  As shown in FIG. 8, an upstream portion of the inflow port 41 is disposed in the top surface layer member M1. In the inflow layer member M2, the downstream side portion of the inflow port 41 and the main body portion 42a of the inlet side flow path 42 are disposed. In the distribution layer member M3, the first to seventh measuring connections 42b to 42h of the inlet-side flow passage 42, the pull-in connections 42i, and the distributing porous medium 42j are disposed. In the determination layer member M4, first to seventh measurement channels 50 to 56, first to seventh porous media 64 to 70 for determination, and an upstream portion 72a of the lead-in channel 72 are disposed. In the containing layer member M5, the first to seventh measuring sections 43 to 49, the first to seventh measuring air passages 57 to 63, the leading section 71, the downstream portion 72b of the leading channel 72, and the leading section A porous medium 73 is disposed.

  The distribution porous medium 42j of the inlet side flow path 42 is disposed to correspond to the main body 42a of the inlet side flow path 42 in the distribution layer member M3. The first to seventh measuring connections 42b to 42h and the drawing connection 42i of the inlet side flow passage 42 are formed to penetrate the distribution layer member M3 in the thickness direction around the distribution porous medium 42j. . The first to seventh metering connections 42b to 42h and the pull-in connections 42i extend radially from the distributing porous medium 42j. One longitudinal ends of the first to seventh measurement connections 42b to 42h and the lead-in connection 42i are connected to the distribution porous medium 42j. The first to seventh measurement channels 50 to 56 and the drawing channel 72 are formed to penetrate the determination layer member M4 in the thickness direction.

  In addition, as shown by the arrow F in FIGS. 11 to 13, in the containing layer member M5, in the forward flow direction, the liquid L along the planar direction of the containing layer member M5 is the first to seventh measuring sections 43 to 43, respectively. In the direction from the downstream side portion 72 b of the flow channel 49 and the suction flow channel 72 to the first to seventh measurement air flow channels 57 to 63 and the flow-in section 71.

  In more detail, the assay device may be configured as follows. As shown in FIG. 8, the inflow port 41 is formed to penetrate the top surface layer member M1 and the inflow layer member M2 in the thickness direction. The main body portion 42a of the inlet-side flow passage 42 is formed to penetrate the inflow layer member M2 in the thickness direction continuously with the inflow port 41 in the thickness direction.

  The first to seventh measuring connections 42b to 42h and the drawing connection 42i of the inlet side flow passage 42 are circumferential directions of the substantially circular distribution porous medium 42j around the distribution porous medium 42j. Are spaced apart from one another. The first to seventh metering connections 42b to 42h and the lead-in connections 42i are formed to penetrate the distribution layer member M3 in the thickness direction. The first to seventh measurement connection portions 42b to 42h are sequentially arranged in the circumferential direction. The lead-in connection 42i is located between the first and seventh metering connections 42b and 42h.

  As shown in FIG. 10, the first to seventh measurement channels 50 to 56 correspond to the other end portions of the first to seventh measurement connection portions 42b to 42h in the longitudinal direction, respectively, in the determination layer member M4. Be placed. Although not particularly illustrated, the upstream side portion 72a of the pull-in channel 72 is disposed in the determination layer member M4 so as to correspond to the other end in the longitudinal direction of the pull-in connection portion 42i.

  As shown in FIG. 8 again, the upstream portions 72a of the first to seventh metering channels 50 to 56 and the inlet channel 72 are formed to penetrate the determination layer member M4 in the thickness direction. The first to seventh measuring sections 43 to 49, the first to seventh measuring air passages 57 to 63, the leading section 71, and the downstream portion 72b of the leading channel 72 penetrate the containing layer member M5 in the thickness direction. Formed as. The top and bottom surfaces of each of the first to seventh measuring sections 43 to 49, the drawing section 71, and the downstream portion 72a of the drawing channel 72 are respectively defined by the determination layer member M4 and the bottom layer member M6. The first to seventh measuring sections 43 to 49 and the downstream portion 72b of the drawing channel 72 are formed substantially in a straight line.

  The upstream end portions in the longitudinal direction of the first to seventh measurement sections 43 to 49 are disposed in the accommodation layer member M5 to correspond to the first to seventh measurement channels 50 to 56 of the determination layer member M4, respectively. Ru. The upstream end portion in the longitudinal direction of the downstream portion 72b of the lead-in channel 72 is disposed in the accommodation layer member M5 so as to correspond to the upstream portion 72a of the lead-in channel 72 of the determination layer member M4. The longitudinally downstream end of the downstream portion 72 b of the inlet channel 72 is connected to the inlet section 71. The first to seventh measuring sections 43 to 49 and the downstream portion 72b of the drawing channel 72 extend radially.

  The top and bottom surfaces of portions other than the connection portions 57a to 63a in the respective metering air passages 57 to 63 are respectively defined by the determination layer member M4 and the bottom layer member M6. The top and bottom surfaces of the connection portions 57a to 63a in each of the metering air passages 57 to 63 are defined by the top and bottom adhesive tapes N1 and N2, respectively. The adhesive (not shown) of the adhesive tapes N1 and N2 is positioned on the top and bottom surfaces of the connection portions 57a to 63a. As a result, the connection portions 57a to 63a of the respective measurement air passages 57 to 63 have hydrophobicity. The adhesive can be selected to have a contact angle greater than 90 degrees. In particular, it is more preferable that the three surfaces of the connection portions 57a to 63a of the measurement air passages 57 to 63 be hydrophobic. That is, although air can pass through the connection portions 57a to 63a, the liquid L can not substantially pass through the connection portions 57a to 63a. Alternatively, a hydrophobic substance layer other than the adhesive may be provided on at least one of the top surface and the bottom surface of the connection to impart hydrophobicity to the measurement air passage.

  Furthermore, each of the first to seventh metering air passages 57 to 63 is formed substantially in a straight line. The connection portions 57a to 63a of the first to seventh measurement ventilation paths 57 to 63 are connected to the downstream end portions in the longitudinal direction of the first to seventh measurement sections 43 to 49, respectively. The first to seventh measurement air passages 57 to 63 extend radially to be continuous with the first to eighth measurement sections 43 to 49, respectively.

  As shown in FIG. 10, the first to seventh porous media for determination 64 to 70 are formed corresponding to the first to seventh measurement channels 50 to 56, respectively. The first to seventh porous media for determination 64 to 70 are configured to be able to block the passage of air in the first to seventh measurement channels 50 to 56, respectively. In other words, it is preferable that the first to seventh measurement flow passages 50 to 56 are closed by the porous media 64 to 70 for the first to seventh determinations, respectively.

  As shown in FIG. 9, the volume W18 of the drawing-in section 71 may be larger than the sum of the first to seventh measurement volumes W11 to W17. The pull-in porous medium 73 has a main body 73 a disposed in the pull-in section 71, and a protrusion 73 b protruding from the pull-in section 71 to the downstream portion 72 b of the pull-in channel 72. In particular, the main body portion 73 a of the porous drawing-in medium 73 may be disposed to occupy the drawing-in section 71. The projecting portion 73 b can be configured to urge to draw the liquid L of the drawing flow channel 72 into the drawing section 71.

  Furthermore, as shown in FIGS. 8 and 9, the assay device comprises seven transparent determination windows 74 and 75 formed on the top surface layer member M1 corresponding to the seven determination porous media 64 to 70, respectively. , 76, 77, 78, 79, 80 may be provided. Hereinafter, as necessary, the seven determination windows will be referred to as first, second, third, fourth, fifth, sixth, and seventh determination windows, respectively. In this case, the inflow layer member M2 is transparent. The assay device may also have a transparent drop-in window 81 formed in the top layer M1 corresponding to the upstream portion 72a of the drop channel 72. In the top surface layer member M <b> 1, portions other than the first to seventh determination windows 74 to 80 and the drawing window 81 may be opaque. When the top surface layer member M1 is transparent, the first to seventh determination window portions and the pull-in window portion may not be provided.

  Referring to FIG. 8, in the process of producing such an assay device, the top surface layer member M1, the inflow layer member M2, the distribution layer member M3, the determination layer member M4, the accommodation layer member M5, and the bottom layer member M6 When arranging so as to sequentially laminate, as described above, the porous media for distribution 42j, the first to seventh porous media for determination 64 to 70, the porous media for drawing 73, the top surface side, and The bottom side adhesive tapes N1 and N2 are disposed. Thereafter, adjacent ones of the top surface layer member M1, the inflow layer member M2, the distribution layer member M3, the determination layer member M4, the containing layer member M5, and the bottom surface layer member M6 are adhered to each other.

[About setting of concentration rate of porous medium for judgment]
The concentration ratio of the porous media for determination 64 to 70 according to the present embodiment can be set in the same manner as in the first embodiment.

[Fluid control of assay device]
The fluid control of the assay device according to the present embodiment will be described with reference to FIGS. As shown in FIG. 11, when the liquid L is continuously supplied to the inflow port 41 in the assay device, first, the liquid L flows from the inflow port 41 to the main portion 42a of the inlet channel 42 based on the lateral flow. It flows through to the porous media for distribution 42j. When the fluid L reaches the distributing porous medium 42j, it is applied to the first to seventh measuring connections 42b to 42h and the drawing connection 42i at substantially the same timing based on the capillary force of the distributing porous medium 42j. Distributed.

  The liquid L distributed to the first to seventh measuring connections 42b to 42h flows to the first to seventh measuring channels 50 to 56, respectively, and to the porous media 64 to 70 for the first to seventh determinations, respectively. Flow. Furthermore, when the liquid L reaches the first to seventh judgment porous media 64 to 70, the liquid L is subjected to the first to seventh judgments based on the capillary force of the first to seventh judgment porous media 64 to 70, respectively. It flows into the seventh weighing section 43-49.

  Thereafter, as shown in FIG. 12, the first to seventh measuring sections 43 to 49 and the first to seventh measuring channels 50 to 56 are filled with the liquid L. In a state where the first to seventh measuring sections 43 to 49 and the first to seventh measuring channels 50 to 56 are filled with the liquid L, the first to seventh porous media 64 to 70 for determination are respectively the first to seventh. The color is changed according to the amount of the sample contained in the liquid L in an amount corresponding to the first to seventh measurement volumes W11 to W17.

  First, the liquid L distributed to the suction connection portion 42i flows in the forward flow direction through the suction passage 72 based on the lateral flow. After the first to seventh measuring sections 43 to 49 and the first to seventh measuring channels 50 to 56 are filled with the liquid L, when the liquid L reaches the drawing porous medium 73, the drawing porous medium The pull-in action of drawing into the draw-in compartment 71 is initiated on the basis of the capillary force of 73.

  As shown in FIG. 13, the inlet porous medium 73 draws in the liquid L remaining in the inlet side flow passage 42 and the inlet passage 72. Then, the liquid L in which the porous media for drawing 73 remains is held in the drawing section 71, and the liquid L filled in the first to seventh measuring sections 43 to 49 as described above is respectively the first to the fourth. The liquid L held as it is by the porous media for determination 7 to 70 for determination and filled in the first to seventh measurement channels 50 to 56 is also determined by the porous media for 64 for determination for first to seventh, respectively. It is kept as it is. As a result, it is possible to accurately measure the liquid L in a desired amount corresponding to each of the measurement volumes W11 to W17, and to accurately determine the sample concentration by each of the determination porous media 64 to 70.

[About concentration determination of assay device]
The fluid control of the assay device according to the present embodiment will be described. A state in which all of the first to seventh measuring sections 43 to 49 and the first to seventh measuring channels 50 to 56 are filled with the liquid L because the first to seventh measuring volumes W11 to W17 are different from each other In each of the first to seventh determination porous media 64 to 70, the degree of color change differs depending on the first to seventh measurement volumes W11 to W17 and the sample concentration. More specifically, the hue, saturation, lightness or luminance of the first to seventh porous media for determination 64 to 70 respectively correspond to the first to seventh measurement volumes W11 to W17 and the sample concentration. Will be different. For example, when the first to seventh measurement volumes W11 to W17 decrease sequentially, all of the first to seventh measurement sections 43 to 49 and the first to seventh measurement channels 50 to 56 have predetermined sample concentrations. In the state of being filled with a certain liquid L, the degree of color change of the porous media 64 to 70 for the first to seventh determinations will sequentially decrease.

  As described above, the basic configuration of the assay device according to the present embodiment can be defined in the same manner as the basic configuration of the assay device according to the first embodiment, and the basic configuration of the assay device An effect similar to the effect based on the basic configuration of such an assay device can be obtained.

  Furthermore, in the specific configuration of the assay device according to the present embodiment, the assay device has a laminated structure including a plurality of layer members M1 to M6, and liquid in the direction from the front surface to the back surface of the laminated structure L is configured to feed L, and the inlet side flow passage 42 includes a main body 42a extending from the inflow port 41, and a plurality of measurement connection portions 42b to 42h that respectively connect the main body 42a to the plurality of measurement flow passages 50 to 56. A suction connecting portion 42i for communicating the main body portion 42a with the suction flow path 72, and suction capable of distributing the liquid L sent from the main body portion 42a to the plurality of measuring connecting portions 42b to 42h and the drawing connecting portion 42i And the inlet channel 72 has an upstream portion 72a and a downstream portion 72b located downstream in the forward flow direction with respect to the upstream portion 72a, The structure includes an inflow layer member M2 in which the main body portion 42a of the inflow port 41 and the inlet side flow channel 42 is disposed, a plurality of measurement connection portions 42b to 42h of the inlet side flow path 42, a lead in connection portion 42i, and a distribution porous Quality medium 42 j, and a distribution layer member M3 positioned closer to the back surface with respect to the inflow layer member M2, a plurality of measurement flow channels 50 to 56, a plurality of judgment porous media 64 to 70, and a suction flow channel A determination layer member M4 that has the upstream portion 72a of 72 and is positioned closer to the back surface with respect to the distribution layer member M3, a plurality of measurement sections 43 to 49, a plurality of measurement air passages 57 to 63, and a drawing section 71, The distribution porous medium 42 j includes the downstream side portion 72 b of the lead-in flow path 72, and the accommodation layer member M 5 positioned closer to the back surface with respect to the judgment layer member M 4. Main unit 4 with distribution layer member M3 a plurality of metering connections 42b-42h and pull-in connections 42i are connected to the distribution porous medium 42j, and the distribution layer member M3 is arranged around the distribution porous medium 42j. A plurality of metering channels 50 to 56 and an upstream side portion 72a of the drawing channel 72 are formed to penetrate the determination layer member M4.

  Therefore, as described in the fluid control of the above-mentioned assay device, if the operation to continuously supply the liquid L to the inflow port 41 is performed, the liquid L can be reliably guided to each of the measurement sections 43 to 49. In addition, it is possible to accurately measure the desired amount corresponding to each of the measurement volumes W11 to W17. Therefore, the operation of the assay device can be simplified, the accuracy of the concentration determination can be improved, and the control performance of the liquid can be improved.

  Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, and the present invention can be modified and changed based on the technical idea thereof.

  The assay device according to the present invention can be applied to a medical device, an in vitro diagnostic agent, POCT, an environmental measurement system, a physicochemical device, or a research reagent.

1 inlet, 2 inlet side channel, 2a to 2d first to fourth measuring branch, 2e downstream end, 3 to 6 first to fourth measuring section, 7 to 10 first to fourth measuring channel , 11 to 14 first to fourth measurement air passages, 15 to 18 first to fourth porous media for judgment, 19 lead-in sections, 20 lead-in channels, 20 a upstream end, 21 lead-in porous media, L Liquid 2g Aeration branch, 31 Inflow porous medium, 32 Inlet side air passage 41 Inlet, 42 Inlet side flow passage, 42a Main body, 42b to 42h 1st to 7th measuring connections, 42i Leading connections, 42j Porous medium for distribution, 43 to 49 first to seventh measuring section, 50 to 56 first to seventh measuring channel, 57 to 63 first to seventh measuring air passage, 64 to 70 first to seventh determination Porous media, 71 inlet section, 72 inlet channel, 72a upstream side, 72b downstream side, 73 pulling Use porous media, M2 inflow layer member, M3 distribution layer member, M4 determination layer member, M5 encasing layer member, M6 bottom layer member

Claims (5)

An assay device configured to be able to determine the concentration of an analyte in a liquid, comprising:
An inlet configured to receive the liquid;
An inlet side channel extending from the inlet;
A plurality of metering compartments configured to be capable of containing the liquid;
A plurality of metering channels each branched from the inlet channel and connected to the plurality of metering sections;
A plurality of metering vents connected to the plurality of metering compartments to be hydrophobic and to allow air to pass therethrough;
And a plurality of determination porous media disposed in each of the plurality of metering channels,
The volumes of a plurality of combinations formed by combining the plurality of measuring sections respectively connected to the plurality of measuring channels are different from each other,
An assay device, wherein each determining porous medium is configured to change its color in response to the amount of analyte in the liquid passing therethrough. A suction compartment configured to be capable of containing the liquid;
A drawing channel connecting the inlet side channel and the drawing section;
The assay device of claim 1, further comprising: a porous withdrawal medium disposed in the withdrawal compartment. The downstream end of the inlet channel and the upstream end of the inlet channel are connected,
The assay device according to claim 2, wherein the plurality of measurement flow channels are branched from the inlet flow channel sequentially in a direction from upstream to downstream of the inlet flow channel. An inflow porous medium disposed corresponding to the inflow port;
The assay device according to claim 3, further comprising: an inlet-side air passage having a hydrophobicity and being branched from the air flow branch located between the inlet and the measurement branch closest to the inlet. The assay device has a laminated structure composed of a plurality of layer members, and is configured to be able to send the liquid in a forward flow direction from the front surface to the back surface of the laminated structure.
The inlet side flow passage includes a main body portion extending from the inflow port, a pull-in connection portion connecting the main body portion to the pull-in flow passage, and a plurality of metering connections respectively connecting the main body portion to the plurality of measurement flow paths A dispensing porous medium configured to be aspirable to dispense liquid delivered from the body to the lead-in connection and the plurality of metering connections;
The lead-in channel has an upstream portion and a downstream portion located downstream of the forward flow direction with respect to the upstream portion;
The laminated structure is
An inflow bed member in which a main body of the inflow port and the flow path on the inlet side are disposed;
A distribution layer member on which the inlet connection of the inlet channel, a plurality of metering connections, and a porous medium for distribution are disposed, and located closer to the back surface with respect to the inflow layer member;
A determination layer member on which the upstream side portion of the lead-in flow passage, the plurality of measurement flow passages, and the plurality of determination porous media are disposed, and which are positioned closer to the back surface with respect to the distribution layer member;
A downstream portion of the lead-in channel, the lead-in section, the plurality of metering sections, the porous porous medium for lead-in, and the plurality of metering air channels are disposed, and are positioned closer to the back surface with respect to the determination layer member Containing layer members and
The distribution porous medium of the inlet side channel is arranged to correspond to the main body of the inlet side channel at the distribution layer member,
The inlet connection and the metering connection of the inlet channel are formed to connect to the distributing porous medium and to penetrate the distribution layer member around the distributing porous medium.
The assay device according to claim 2, wherein an upstream portion of the lead-in channel and the plurality of metering channels are formed to penetrate the determination layer member.

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