Analysis devices

Abstract

To provide an analytical device that can rapidly separate specific components from a liquid sample. [Solution] An analytical device is provided having a first sheet and a second sheet on which a portion of the first sheet overlaps. The first sheet is located upstream of the second sheet with respect to the direction in which the liquid sample flows in the analytical device, and the analytical device is configured to have a fluid connection part through which the sample that has permeated the first sheet permeates into the flow path of the second sheet, wherein the second sheet is located above the first sheet, and the flow path of the second sheet extends downstream from the downstream end of the fluid connection part.

Description

Technical Field

[0001] The present disclosure relates to an analysis device.

Background Art

[0002] In recent years, the development of microchannel devices (also referred to as analysis devices in the present invention) that can perform biochemical analyses efficiently (with a small amount of sample, rapidly, and conveniently) within a single chip by utilizing micro-sized fine flow channels has attracted attention in a wide range of fields. Specifically, they are drawing attention in various fields such as medical care, drug discovery, healthcare, environment, and food, in addition to biochemical research.

[0003] A paper-based micro analytical chip uses an inexpensive material such as paper or cloth as a base material, and can drive a specimen or a test liquid by utilizing the capillary phenomenon of the material itself. For this reason, compared with conventional devices, the paper micro analytical chip has advantages such as being lightweight, easy to carry, low cost, no need to use a power source, easy to handle, and high disposability.

[0004] Due to these advantages, paper micro analytical chips are expected to be used as testing devices for medical activities in developing countries, remote areas with inadequate medical facilities, and disaster sites, as well as at airports and other locations where the spread of infectious diseases must be contained at the border.

[0005] In addition, due to their low cost and ease of handling, paper micro analytical chips are also attracting attention as healthcare devices that can manage and monitor one's own health condition.

[0006] Furthermore, by utilizing paper microanalysis chips, maintenance of the device is unnecessary, making it possible for anyone, anywhere (even in locations without power) to easily and inexpensively perform point-of-care (POC) diagnostics. Therefore, research and development of paper microfluidic devices targeting various infectious diseases, specific diseases, and healthcare is currently underway at research institutions worldwide.

[0007] As paper microfluidic chips, those are known that have hydrophilic or porous fluidic regions surrounded by hydrophobic fluidic channel walls located inside or on the substrate.

[0008] Paper microfluidic chips have configurations that allow samples to penetrate in the thickness direction of the porous substrate (vertical flow) and configurations that allow samples to penetrate horizontally (lateral flow). Reagents for colorimetric or fluorescence testing are placed in a portion of the flow path, or electrodes for electrochemical testing are placed there.

[0009] The role of a flow channel is to guide the sample to the reagent at the end of the channel or to the electrode. It can also filter the sample along the way or react it with other reagents. By branching the flow channel, multiple tests can be performed simultaneously.

[0010] In the field of clinical diagnosis, many qualitative and quantitative measurements utilize bodily fluid components such as blood and urine. In clinical trials measuring blood components, blood is often separated into blood cell components and serum or plasma (hereinafter referred to as "plasma," etc.) components, and these plasma components are then used for measurement. Typically, after collecting blood, the plasma, etc., is separated by centrifugation before the sample is used for measurement. To simplify point-of-care (POC) diagnosis, techniques have been disclosed for separating small amounts of blood into blood cells and plasma, etc.

[0011] For example, a method for obtaining plasma from blood is disclosed, which involves using glass fiber filter paper having a specific pore size and density, or by laminating the glass fiber filter paper with other filters (Patent Document 1). An analytical tip is also disclosed, which has a configuration in which multiple through-holes are arranged in a part of the flow path of a porous substrate (Patent Document 2). [Prior art documents] [Patent Documents]

[0012] [Patent Document 1] Special Publication No. 6-64054 [Patent Document 2] International Publication No. 2020 / 196817 [Overview of the Initiative] [Problems that the invention aims to solve]

[0013] This disclosure aims to provide an analytical device for efficiently recovering plasma and other materials from minute whole blood samples that can be used for multi-parameter analysis rapidly and without centrifugation. [Means for solving the problem]

[0014] This disclosure is, An analytical device for analyzing liquid samples, The analysis device has a first sheet and a second sheet on which a portion of the first sheet overlaps. The first sheet has a first base material, The first substrate is a porous substrate containing glass fibers, The second sheet has a second base material, The second substrate is a porous substrate containing cellulose, The second sheet has channel walls formed by filling the pores of the second substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. The first sheet is located upstream of the second sheet, with reference to the direction in which the liquid sample flows in the analytical device. The analysis device is configured to be provided with a fluid connection part that allows the specimen having permeated through the first sheet to permeate into the flow channel of the second sheet, In the fluid connection part, the second sheet is disposed on the upper side of the first sheet, The flow channel of the second sheet extends further downstream than the downstream end of the fluid connection part. Effects of the Invention

[0015] By using the analysis device of the present disclosure, a specific component (for example, plasma) can be efficiently separated and analyzed from a liquid specimen (for example, a whole blood sample). Brief Description of the Drawings

[0016] [Figure 1] They are a top view (a) and a cross-sectional view (b) of the analysis device of Example 1. [Figure 2] They are a top view (a) and a cross-sectional view (b) of the analysis device of Example 1. [Figure 3] They are a top view (a) and a cross-sectional view (b) of a comparative example. [Figure 4] They are a top view (a) and a cross-sectional view (b) of the device form of Example 2. [Figure 5] They are a top view (a) and a cross-sectional view (b) of the device form of Example 3. [Figure 6] They are a top view (a) and a cross-sectional view (b) of the device form of Example 4. [Figure 7] They are a top view (a) before cutting and a top view (b) after cutting of the device form of Example 5. [Figure 8] They are a top view (a), an enlarged top view (b), and cross-sectional views (c) to (e) of the device form of Example 6. [Figure 9] They are cross-sectional views (a) and (b) of the device form of Example 6. [Figure 10] It is a cross-sectional view of the device form of Example 6. [Figure 11] Cross-sectional view of the device form of Example 7 [Modes for carrying out the invention]

[0017] Hereinafter, exemplary embodiments of this disclosure will be described with reference to the drawings. Note that the following embodiments are illustrative and do not limit this disclosure to the content of these embodiments. Furthermore, elements not necessary for explanation have been omitted from each drawing. [Examples]

[0018] The following describes the examples. <Example 1> <Configuration of the analysis device> Figure 1 illustrates the structure of the first sheet 1 and the second sheet 2 in the analytical device of this disclosure.

[0019] Figure 1(a) is a top view of the analysis device 100, and Figure 1(b) is a cross-sectional view of the analysis device 100. Figure 2 shows the analysis device 100 as shown in Figure 1, as well as the analysis device 100 covered with a cover layer 24.

[0020] The analysis device 100 has a first sheet 1 and a second sheet 2 on which a portion of the first sheet 1 overlaps.

[0021] The first sheet 1 has a first base material, and the first base material is a porous base material containing glass fibers.

[0022] The second sheet 2 has a second base material, and the second base material is a porous base material containing cellulose.

[0023] The second sheet 2 has a channel wall 22 formed by filling the pores of the second substrate with a hydrophobic material, and a channel 21 formed by being restricted by the channel wall 22.

[0024] The first sheet 1 is located upstream of the second sheet 2, with reference to the direction in which the liquid sample flows in the analytical device (indicated by the arrow in the figure). The analytical device is configured so that the sample that has permeated the first sheet 1 then permeates into the flow path 21 of the second sheet 2. At the fluid connection point where the sample that has permeated the first sheet permeates into the flow path of the second sheet, the second sheet 2 is positioned above the first sheet 1.

[0025] In the diagram, 11 represents the flow path of the first sheet 1 (sometimes called the first flow path), 21 represents the flow path of the second sheet 2 (sometimes called the second flow path), 23 represents the storage section which is also part of the flow path, and 3 represents the dispensing section which is also part of the flow path.

[0026] <Porous base material> Both the first sheet 1 and the second sheet 2 have a porous substrate. The porous substrate should have an appropriate porosity and generate capillary action in the liquid. It may have porosity such as open bubbles, nanofibers, or a mesh-like structure inside, and may be made of filter paper, plain paper, fine paper, watercolor paper, Kent paper, resin, glass, inorganic substrate, cloth, metal paper, etc. The porosity can be appropriately selected depending on the purpose, but 20% to 90% is preferred. If the porosity exceeds 90%, the strength of the substrate may not be maintained, and if it is less than 20%, the permeability of the sample liquid tends to decrease.

[0027] The porous substrate is preferably hydrophilic in order to facilitate the diffusion of water-containing biological fluids, such as blood, urine, and saliva, as sample liquids (liquid specimens), into the substrate. Preferably, the first sheet 1 is a porous substrate containing glass fibers, and the second sheet 2 is a porous substrate containing cellulose.

[0028] Porous substrates can be selected as appropriate depending on the purpose, but a thickness of 0.05 mm to 0.8 mm is preferable. 0.05 mm to 0.8 mm is a common thickness. If the average thickness is less than 0.05 mm, the strength of the substrate may not be maintained.

[0029] The porous substrate used in this embodiment is as follows. As the first sheet 1, LF1 filter paper manufactured by Cytiva, which is a glass fiber-containing filter paper, was used. In this embodiment, LF1 filter paper was used, but depending on the application, other known glass fiber-containing filter papers such as MF1 filter paper or VF2 filter paper may be used. In addition, LF1 filter paper or MF1 filter paper may be used that has been coated, for example, to improve hydrophilicity, in order to improve plasma separation performance.

[0030] The second sheet 2 was a porous substrate made of cellulose fiber filter paper with a void ratio of 75% and a thickness of 0.5 mm.

[0031] <Materials for forming channel walls> The channel wall forming material can be a thermoplastic resin that penetrates into the porous substrate when melted by heat, and preferably, a thermoplastic resin containing wax (oil or fat) can be used.

[0032] The thermoplastic resin is not particularly limited, and any known thermoplastic resin can be used. For example, polyester, vinyl resins, acrylic resins, styrene-acrylic resins, polyethylene, polypropylene, polyolefins, ethylene-vinyl acetate copolymer resins, and ethylene-acrylic acid copolymer resins can be used.

[0033] The wax (oil) used is not particularly limited, and any known wax can be used. For example, natural ester waxes, hydrocarbon waxes, and amide waxes can be used.

[0034] In this example, channel walls were formed by impregnating a porous substrate with a styrene-acrylic resin.

[0035] <Sheet layout>

[0036] The arrangement of the first and second sheets will be explained using Figures 1 and 2.

[0037] In the example shown in Figure 1(a), the first sheet 1 is rectangular with a width of 10 mm and a length of 40 mm, and the second sheet 2 is a square piece of paper measuring 50 x 30 mm, with a channel 21 having a storage section 23 surrounded by channel walls 22. As shown in Figure 1(b), a portion of the second sheet 2 is positioned above the sheet 1, and the analytical device is configured with a fluid connection section 41 through which the sample that has permeated the first sheet permeates into the channel of the second sheet. The liquid that has permeated through the first channel 11 permeates into the channel of the second channel 21 at the fluid connection section 41 and continues to flow through the second channel 21.

[0038] As shown in Figure 2, the top and bottom of the first sheet 1 and the second sheet 2 can be covered with a cover layer 24 such as a laminate so that the sheets are in close contact with each other. In this case, a portion of the first sheet 1 on the dispensing surface side that is not laminated can be provided to form the dispensing section 3.

[0039] <Blood filtration and collection process> Blood is dispensed into the dispensing section 3 located upstream of the flow path 11 of the first sheet 1 (the end away from sheet 2). As the blood passes through the porous flow path containing glass fibers, red blood cells and white blood cells are filtered out to form plasma. The plasma passes through the fluid connection section 41 and proceeds through the flow path 21 of the second sheet 2 to the storage section 23. Here, by positioning the second sheet 2 above the first sheet 1, the plasma that has passed through the flow path 11 of the first sheet 1 can be transferred to the flow path 21 of the second sheet 2 by pumping it up. With this pumping configuration, for example, more than a predetermined amount of plasma is gradually supplied to the second sheet 2 over time by gravity, preventing the plasma from overflowing. Also, with this pumping configuration, the blood cell components separated by gravity gradually settle to the bottom side of the first sheet 1, thus preventing contamination of the second sheet 2 with blood cell components. Furthermore, the optimal values ​​for the length of the first sheet 1 and the length (L) of the fluid connection part 41 vary depending on the size of the flow path, the amount of plasma stored in the storage section, and the amount of blood to be dripped. However, in this embodiment, if the length of the first sheet 1 is 40 mm and L is 3 mm or more, blood cell components can be properly separated and the plasma solution can flow smoothly. Also, regarding the width W of the flow path 21 of the fluid connection part 41, considering the latitude during assembly of the fluid connection part 41, it can be larger or smaller than the width of the first sheet 1, and in this embodiment, it is set to 8 mm, which is smaller than the width of the first sheet 1.

[0040] The plasma stored in the storage section 23 can be used for testing by cutting out the storage section 23, for example, with a punch.

[0041] Here, by forming the channel wall 22 of the second sheet 2 with a hydrophobic material, the volume of the storage section can be set to a desired amount, and by filling the storage section with plasma solution, it becomes possible to ensure the quantitative accuracy of the amount of plasma stored in the storage section. Therefore, compared to the case without a channel wall, it becomes possible to analyze a quantitative amount of plasma at all times, thereby improving the accuracy of the test.

[0042] As a comparative example, Figure 3 shows an example in which the flow paths of the first sheet 1 and the second sheet 2 do not overlap, that is, do not have a fluid connection part, and are connected at their end faces. Figure 3(a) is a top view, and Figure 3(b) is a cross-sectional view.

[0043] In this connection configuration, the contact area between the filter papers is smaller compared to the configuration of this embodiment, which can lead to less smooth plasma flow and potential gaps in the liquid filling of the storage section, making it impossible to guarantee quantitative accuracy. This affects the variability of subsequent analysis results and lowers the measurement accuracy.

[0044] As in this embodiment, the first sheet 1 and the second sheet 2 are formed by laminating them together, with a portion of the second sheet 2 positioned above the first sheet 1. By creating an analytical device 100 in which the first channel 11 and the second channel 21 are fluidly connected, the plasma solution separated in the first channel 11 can be smoothly sent to the second channel 21 positioned above it, allowing the storage section to be filled with the liquid with high precision.

[0045] In this embodiment, the first sheet 1 is described as a porous substrate containing glass fibers with the entire substrate acting as a channel. However, the channel 11 of the first sheet 1 may also be a channel formed by filling the porous substrate containing glass fibers with a hydrophobic material to create a channel wall, and being restricted by the channel wall. For example, by providing a channel wall at the end of the first sheet 1, blood leakage from the first sheet can be prevented while it is directed to the channel 21 of the second sheet.

[0046] This disclosure is characterized by having a second sheet 2 which is arranged overlapping a first sheet 1 in part, the second sheet 2 being positioned above the first sheet 1, and further, the flow path 21 of the second sheet 2 extending downstream from the downstream end of the fluid connection portion 41 (the extended portion is indicated by 42). Its operation and effects will be explained.

[0047] By stacking the first sheet 1 on the bottom and the storage section 23 of the second sheet 2 on top, only easily permeable components (e.g., plasma) can permeate into the second sheet 3, while the permeation of less permeable components (e.g., blood cells) into the second sheet 2 can be suppressed. When blood is the sample, at the point when the sample permeates the edge of the first sheet 1, the blood cells, which have a larger mass, permeate to the lower side of the first sheet 1, while a large amount of plasma components permeate to the upper side of the first sheet 1. By positioning the second sheet 2 above the first sheet 1 in this way, it becomes more difficult for blood cells to move to the second sheet 2, minimizing contamination of the storage section 23 with blood cells and enabling more efficient plasma separation.

[0048] In this disclosure, the length L of the fluid connection portion 41 is limited, and only the second sheet 2 has an extended portion 42 that extends downstream. The presence of the extended portion 42 ensures that the plasma flow from the first sheet 1 to the second sheet 2 is uniform and smooth. If the fluid connection portion 41 is made larger, the absolute amount of sample that permeates the first sheet 1 increases, and the amount of sample required for testing increases. Therefore, the configuration in this disclosure increases the plasma recovery efficiency and reduces the amount of sample required. The area ratio of the flow path portion of the second sheet 2 in the fluid connection portion 41 to the total area of ​​the flow path portion of the second sheet downstream from the fluid connection portion 41 is preferably 2 to 49%, and more preferably 4 to 20%. Also, from a similar viewpoint, the length L of the fluid connection portion 41 is preferably 14 mm or less. In order to properly separate blood cell components, L is preferably 3 mm or more, so L is preferably 3 mm to 14 mm. In this embodiment, for example, L can be 4 mm and the above area ratio can be 14%.

[0049] <Example 2> The analytical device of this embodiment is configured such that a notch is provided in the second sheet 2 to match the shape of the first sheet 1, and the first sheet 1 is fitted into the notch, so that only the tip portion of the first sheet 1 overlaps with the second sheet 21. A flow channel wall 22 is formed around the notch in the first sheet 1. A top view of this analytical device is shown in Figure 4(a), and a cross-sectional view at W in Figure 4(a) is shown in Figure 4(b).

[0050] With this configuration, positioning the first sheet becomes easier.

[0051] <Example 3> The analytical device of this embodiment is an analytical device in which a cover layer (upper laminate layer) 24 is provided on the surface of a second sheet 2 via an adhesive layer. In this analytical device, there is no region on the surface of the first sheet 1 in which an adhesive layer is directly formed. That is, in the region on the first sheet 1 in which the cover layer 24 is formed, the second sheet 2 is present between the first sheet 1 and the cover layer 24.

[0052] A top view of the analytical device of this embodiment is shown in Figure 5(a), and a cross-sectional view is shown in Figure 5(b).

[0053] If the adhesive layer is applied directly to the surface of the first sheet, the adhesive will penetrate the first sheet, reducing the thickness of the penetration area of ​​the first sheet. With the configuration of this embodiment, the adhesive layer (not shown) comes into contact with the surface of the second sheet, so a cover layer can be provided without reducing the thickness of the penetration area of ​​the first sheet.

[0054] For the cover layer, we used NEION's overlaminate film PET50-L8-KG2. This film consists of a PET film with a thickness of 50 μm to which an acrylic adhesive is applied as an adhesive layer.

[0055] Furthermore, as shown in Figure 5(b), a cover layer (lower laminate layer) 24 can also be provided on the first sheet 1 side, creating an analytical device sandwiched between laminates. In this case, the channel wall 31 of the second sheet is located above the first channel 11 of the first sheet 1, and the cover layer 24 does not directly contact the upper surface of the first sheet 1. For example, the analytical device of this embodiment can be manufactured by using Fujitex Corporation's pouch laminator F360 and laminating with a sheet feed speed set to 22.8 mm / second (cold lamination).

[0056] Furthermore, the top surface of the analytical device may be covered with a peel-off seal. By making it peel-off, the sample can be dispensed with the peel-off seal removed during dispensing, and the seal can be put back on after dispensing is complete, thus preventing the sample from being touched by hands. For example, as a peel-off seal, Nakagawa Chemical's Retack Sheet (63 μm thick, with an acrylic adhesive on a polypropylene base) can be used.

[0057] Furthermore, configurations that include a cover layer or a peel seal can be applied to other embodiments as needed.

[0058] <Example 4> The analytical device of this embodiment has multiple fluid connection parts 41, each of which surrounds a dispensing section 3 formed on the first sheet 1. Furthermore, there may be multiple fluid connection parts 41 and multiple storage sections 23 connected to them, in which case the multiple storage sections 23 may also surround the dispensing section 3. A top view of this analytical device is shown in Figure 6(a), and a cross-sectional view is shown in Figure 6(b). In this example, four fluid connection parts 41 and four connected storage sections 23 are provided for one dispensing section 3 (only two of them are shown in Figure 6(b)). The multiple fluid connection parts 41 surround the dispensing section 3. The multiple storage sections 23 also surround the dispensing section 3. Note that in Figures 6(a) and (b), an example is shown where the multiple fluid connection parts 41 are equidistant from the dispensing section 3, but they do not have to be equidistant.

[0059] In Figures 6(a) and 6(b), a cover layer 24 is provided on the upper surface of the second sheet 2.

[0060] This configuration allows for a shorter flow path 11 compared to the configuration in Example 1, thereby reducing the time required for inspection and also allowing for a smaller overall device size.

[0061] <Example 5> The analytical device of this embodiment is an analytical device that facilitates the cutting of a portion of the analytical device. A configuration that facilitates cutting should be provided in the area into which the sample penetrates. The location of such a configuration is not particularly limited, as long as it is upstream of the storage section 23 of the second sheet.

[0062] One example of a configuration that facilitates cutting is a cutting aid section 26. The cutting aid section 26 may be provided on the first sheet and / or the second sheet, but when a cover layer 24 is provided, it is preferable from the viewpoint of not obstructing the flow of the sample to provide the cutting aid section 26 on the cover layer 24 and not on the first and second sheets. Specific examples of the cutting aid section include perforations and notches. If the cover layer has perforations, it can be cut out integrally with the first and second sheets. The perforations can be configured by making a cut of 3 mm, then separating it by 1 mm, and then making another cut of 3 mm.

[0063] If the analytical device has a first sheet that protrudes relative to the second sheet, perforations can be added so that the protruding portion can be cut off. Figure 7(a) shows a top view of the analytical device of this embodiment before cutting, and Figure 7(b) shows a top view after cutting.

[0064] In this embodiment of the analytical device, it is possible to prevent components other than the desired component in the sample from gradually permeating and reaching the storage section at a later rate than the desired component.

[0065] Furthermore, the configuration of this embodiment can also be applied to configurations in which the second sheet is positioned below the first sheet in the fluid connection section, or to configurations in which the flow path of the first sheet and the flow path of the second sheet are connected at their end faces.

[0066] <Example 6> The analytical device of this embodiment has a configuration in which a vertical hole (through hole) 28, open to the outside, is provided in the thickness direction of the analytical device in the region into which the sample penetrates. This analytical device is shown in Figures 8(a), (b), and (c). The position of the vertical hole (through hole) 28 is not particularly limited as long as it is upstream of the storage section 23 of the second sheet, but it is preferable that it be located downstream when the region into which the sample penetrates is divided into two. Particularly preferable, the vertical hole (through hole) 28 is provided in the fluid connection section 41.

[0067] By providing the vertical holes 28, the flow of the sample is altered, preventing components other than the desired components from reaching the storage area later than the desired components. Furthermore, in a configuration where the cover layer 24 is provided on the second sheet, volatilization from the sample is suppressed, so even components that penetrate slowly tend to penetrate steadily. However, in a configuration with vertical holes 28, volatilization from the sample occurs, suppressing the penetration of components that penetrate slowly.

[0068] For example, in the case of an analytical device that uses blood as a sample and separates and collects plasma, the vertical pores can suppress the penetration of blood cells, thereby preventing blood cells from contaminating the storage area.

[0069] The vertical holes are preferably 0.1 to 0.5 mm in diameter, with a spacing of 0.5 to 1.5 mm between them.

[0070] Furthermore, this configuration can also be applied to configurations where the second sheet is positioned below the first sheet in the fluid connection section, or where the flow path of the first sheet and the flow path of the second sheet are connected at their end faces.

[0071] Furthermore, in this embodiment, the vertical hole penetrates the entire analytical device, but the vertical hole may penetrate only one sheet or only the cover layer. Note that a vertical hole refers to a long, narrow hole (pinhole), such as a pinhole made with a needle. Other types of holes, such as those formed by laser processing, may also be used. There are several patterns for configurations with vertical holes, and the effect differs depending on the configuration. For example, there are the following patterns. (I) A vertical hole 28 is made from the upper side of the cover layer 24, through the first sheet 1 and the second sheet 2, down to the lower cover layer 24 (Figure 8(c)). (II) Do not make holes in either the lower or upper cover layer 24 (Figures 8(d), (e)). (III) Only the upper cover layer 24 and the second sheet 2 are provided with holes (Figure 9(a)). (IV) Only the lower cover layer 24 and the first sheet 1 are provided with vertical holes 28 (Figure 9(b)).

[0072] Here, there is no significant difference in the effect of stopping blood cells between configurations (I) and (II). This is thought to be because the presence of vertical holes that penetrate both the first and second sheets and are open to the outside promotes drying throughout the entire thickness of the sheet. In configurations (III) and (IV), although the sheets with vertical holes are effective in promoting drying, the effect is halved because there is no drying promotion in the sheets without holes. Therefore, configurations (I) or (II) are preferred.

[0073] When creating vertical holes, the holes may be made when each sheet and cover layer is stacked, or the holes may be made in each sheet and cover layer individually, and the positions of the vertical holes may be aligned during assembly. In the latter case, it is sufficient that the positions of the vertical holes in at least the cover layer and the sheet in contact with the cover layer are aligned, and as shown in Figure 10, the positions of the vertical holes 28 in the first sheet 1 and the second sheet 2 do not necessarily have to be aligned, as long as the vertical holes 28 are present in the fluid connection portion 41. Furthermore, the vertical holes do not necessarily have to be made vertically; for example, they can be made diagonally to increase the cross-sectional area of ​​the drying portion.

[0074] It is preferable to form a vertical hole from the first sheet side using a pointed tool such as a needle while the first and second sheets are stacked. By forming a vertical hole while both sheets are stacked, the hole is formed in such a way that one substrate penetrates into the other substrate. Forming a vertical hole from the first sheet side with a needle or the like makes the penetration of the sample from the first sheet to the second sheet smoother. In this embodiment, a vertical hole was formed from the first sheet side using a needle, and the first sheet penetrated approximately 190 μm into the second sheet side at the vertical hole formation site.

[0075] In this embodiment, NEION's overlaminate film PET50-L8-KG2 was used as the cover layer. This film consists of a PET film with a thickness of 50 μm to which an acrylic adhesive is applied as an adhesive layer. Sheet 1 and Sheet 2 were placed on top of each other and laminated by sandwiching them with laminating film. Lamination was performed using Fujitex Corporation's pouch laminator F360 with cold lamination and a sheet feed speed set to 22.8 mm / second.

[0076] Furthermore, the top surface of the analytical device of this disclosure may be covered with a peel seal. The analytical device was covered with a re-tack sheet (63 μm thick, with an acrylic adhesive on a polypropylene base) from Nakagawa Chemical Co., Ltd. Since the peel seal can be opened and closed, the cover covering the dispensing section can be opened to dispense the sample, and after dispensing is complete, the seal can be closed, thus eliminating the need to touch the sample by hand.

[0077] <Example 7> The device of this embodiment is an analytical device in which a cover layer is provided between a first sheet and a second sheet via an adhesive layer, and as shown in Figure 11, the cover layer 24 has vertical holes 28 that penetrate in the thickness direction only. In this configuration, the drying of the sample is suppressed by covering the flow path with the cover layer 24, so that penetration occurs smoothly.

[0078] Furthermore, compared to a configuration where the cover layer 24 does not have vertical pores, the configuration with vertical pores 28 (Figure 11) promotes drying near the vertical pores 28. Therefore, forming vertical pores allows for faster sample flow.

[0079] When the sample is blood, the plasma permeates faster than blood cells, and blood cells move more slowly. Therefore, vertical holes are formed in the cover layer to prevent all of the plasma moving through the substrate from drying out. By using vertical holes of an appropriate size, it is possible to stop blood cells midway through the flow path by promoting drying without stopping the permeation of plasma. In this embodiment, vertical holes with a diameter of 1.0 mm were provided in the flow path portion of the fluid connection section, which is 2.5 mm wide, 4.0 mm long, and 0.5 mm thick.

[0080] This embodiment includes the following configuration. (Composition 1) An analytical device for analyzing liquid samples, It has a first sheet and a second sheet in which a part of the first sheet is arranged overlapping, The first sheet has a first base material, The first substrate is a porous substrate containing glass fibers, The second sheet has a second base material, The second substrate is a porous substrate containing cellulose, The second sheet has channel walls formed by filling the pores of the second substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. The first sheet is located upstream of the second sheet, with reference to the direction in which the liquid sample flows in the analytical device. The analytical device is configured to include a fluid connection section through which the sample that has permeated the first sheet permeates into the flow path of the second sheet. In the fluid connection section, the second sheet is positioned above the first sheet. The analytical device is characterized in that the flow path of the second sheet extends downstream from the downstream end of the fluid connection portion. (Configuration 2) The analytical device according to configuration 1, wherein the first sheet has channel walls formed by filling the pores of the first substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. (Composition 3) The analytical device according to configuration 1 or 2, wherein the first sheet has a dispensing section for dispensing the liquid sample. (Composition 4) The analytical device according to configuration 3, having a plurality of fluid connection parts, each of which surrounds the dispensing part. (Composition 5) The analytical device according to any one of configurations 1 to 4, having a cover layer via an adhesive layer on the surface of the first sheet and the surface of the second sheet. (Composition 6) The second sheet has a cover layer on its surface via an adhesive layer, The analytical device according to any one of configurations 1 to 4, wherein an adhesive layer is not provided on the surface of the first sheet. (Composition 7) The analytical device according to any one of configurations 1 to 6, having a cutting assist portion in the region into which the sample penetrates, which assists in cutting off a part of the analytical device. (Composition 8) The analytical device according to configuration 7, wherein the cutting aid is a perforation. (Composition 9) The analytical device according to any one of configurations 1 to 8, wherein a vertical hole open to the outside is provided in the region into which the sample penetrates, in the thickness direction of the analytical device. (Composition 10) An analytical device for analyzing liquid samples, It has a first sheet and a second sheet in which a part of the first sheet is arranged overlapping, The first sheet has a first base material, The first substrate is a porous substrate containing glass fibers, The second sheet has a second base material, The second substrate is a porous substrate containing cellulose, The second sheet has channel walls formed by filling the pores of the second substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. The first sheet is located upstream of the second sheet, with reference to the direction in which the liquid sample flows in the analytical device. The analytical device is configured to include a fluid connection section through which the sample that has permeated the first sheet permeates into the flow path of the second sheet. An analytical device characterized in that the fluid connection portion has a cutting assist portion that assists in cutting off a part of the analytical device. (Composition 11) The analytical device according to configuration 10, wherein the cutting aid is a perforation. (Composition 12) An analytical device for analyzing liquid samples, It has a first sheet and a second sheet in which a part of the first sheet is arranged overlapping, The first sheet has a first base material, The first substrate is a porous substrate containing glass fibers, The second sheet has a second base material, The second substrate is a porous substrate containing cellulose, The second sheet has channel walls formed by filling the pores of the second substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. The first sheet is located upstream of the second sheet, with reference to the direction in which the liquid sample flows in the analytical device. The analytical device is configured to include a fluid connection section through which the sample that has permeated the first sheet permeates into the flow path of the second sheet. An analytical device characterized in that a vertical hole, open to the outside, is provided in the region into which the sample penetrates, in the thickness direction of the analytical device. (Composition 13) The analytical device according to configuration 12, wherein the vertical hole is a through hole that penetrates the entire analytical device. (Composition 14) The analytical device according to configuration 12, wherein the vertical hole is a hole that penetrates the first sheet and the second sheet of the analytical device and at least one of the cover layer on the side in contact with the first sheet or the cover layer on the side in contact with the second sheet. (Composition 15) The analytical device according to configuration 12, wherein the vertical hole penetrates the first sheet and the cover layer on the side in contact with the first sheet, but does not penetrate the second sheet and the cover layer on the side in contact with the second sheet. (Composition 16) The analytical device according to any one of configurations 12 to 15, wherein the vertical hole is located in the fluid connection portion. [Explanation of symbols]

[0081] 1. First sheet 2 Second seat 3. Dispensing section 11. Flow channel (first flow channel) 21. Channel (Second Channel) 22 Flow channel wall 23 Storage section 24 Cover layer 26 Cutting aid 28 Vertical holes (through holes) 41 Fluid connection section 42 Extension

Claims

1. An analytical device for analyzing liquid samples, It has a first sheet and a second sheet in which a part of the first sheet is arranged overlapping, The first sheet has a first base material, The first substrate is a porous substrate containing glass fibers, The second sheet has a second base material, The second substrate is a porous substrate containing cellulose, The second sheet has channel walls formed by filling the pores of the second substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. The first sheet is located upstream of the second sheet, with reference to the direction in which the liquid sample flows in the analytical device. The analytical device is configured to include a fluid connection section through which the sample that has permeated the first sheet permeates into the flow path of the second sheet. In the fluid connection section, the second sheet is positioned above the first sheet. The analytical device is characterized in that the flow path of the second sheet extends downstream from the downstream end of the fluid connection portion.

2. The analytical device according to claim 1, wherein the first sheet has a channel wall formed by filling the pores of the first substrate with a hydrophobic material, and a channel formed by being restricted by the channel wall.

3. The analytical device according to claim 1 or 2, wherein the first sheet has a dispensing section for dispensing the liquid sample.

4. The analytical device according to claim 3, having a plurality of fluid connection parts, each of which surrounds the dispensing part.

5. The analytical device according to claim 1 or 2, wherein a cover layer is provided on the surface of the first sheet and the surface of the second sheet via an adhesive layer.

6. The second sheet has a cover layer on its surface via an adhesive layer, The analytical device according to claim 1 or 2, wherein an adhesive layer is not provided on the surface of the first sheet.

7. The analytical device according to claim 1 or 2, further comprising a cutting assist portion in the region into which the sample penetrates, which assists in cutting off a portion of the analytical device.

8. The analytical device according to claim 7, wherein the cutting aid is a perforation.

9. The analytical device according to claim 1 or 2, wherein a vertical hole open to the outside is provided in the region into which the sample penetrates, in the thickness direction of the analytical device.

10. An analytical device for analyzing liquid samples, It has a first sheet and a second sheet in which a part of the first sheet is arranged overlapping, The first sheet has a first base material, The first substrate is a porous substrate containing glass fibers, The second sheet has a second base material, The second substrate is a porous substrate containing cellulose, The second sheet has channel walls formed by filling the pores of the second substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. The first sheet is located upstream of the second sheet, with reference to the direction in which the liquid sample flows in the analytical device. The analytical device is configured to include a fluid connection section through which the sample that has permeated the first sheet permeates into the flow path of the second sheet. An analytical device characterized in that the fluid connection portion has a cutting assist portion that assists in cutting off a part of the analytical device.

11. The analytical device according to claim 10, wherein the cutting aid is a perforation.

12. An analytical device for analyzing liquid samples, It has a first sheet and a second sheet in which a part of the first sheet is arranged overlapping, The first sheet has a first base material, The first substrate is a porous substrate containing glass fibers, The second sheet has a second base material, The second substrate is a porous substrate containing cellulose, The second sheet has channel walls formed by filling the pores of the second substrate with a hydrophobic material, and channels formed by being restricted by the channel walls. The first sheet is located upstream of the second sheet, with reference to the direction in which the liquid sample flows in the analytical device. The analytical device is configured to include a fluid connection section through which the sample that has permeated the first sheet permeates into the flow path of the second sheet. An analytical device characterized in that a vertical hole, open to the outside, is provided in the region into which the sample penetrates, in the thickness direction of the analytical device.

13. The analytical device according to claim 12, wherein the vertical hole is a through hole that penetrates the entire analytical device.

14. The analytical device according to claim 12, wherein the vertical hole is a hole that penetrates the first sheet and the second sheet of the analytical device and at least one of the cover layer on the side in contact with the first sheet or the cover layer on the side in contact with the second sheet.

15. The analytical device according to claim 12, wherein the vertical hole penetrates the first sheet and the cover layer on the side in contact with the first sheet, but does not penetrate the second sheet and the cover layer on the side in contact with the second sheet.

16. The analytical device according to any one of claims 12 to 15, wherein the vertical hole is located in the fluid connection portion.

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