WO2023048214A1 - Feuille d'échantillonnage, feuille d'inspection et procédé de collecte d'échantillon - Google Patents

Feuille d'échantillonnage, feuille d'inspection et procédé de collecte d'échantillon Download PDF

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Publication number
WO2023048214A1
WO2023048214A1 PCT/JP2022/035338 JP2022035338W WO2023048214A1 WO 2023048214 A1 WO2023048214 A1 WO 2023048214A1 JP 2022035338 W JP2022035338 W JP 2022035338W WO 2023048214 A1 WO2023048214 A1 WO 2023048214A1
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Prior art keywords
sample
driving liquid
channel
sampling
capillary pump
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PCT/JP2022/035338
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English (en)
Japanese (ja)
Inventor
浩二 太田
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三洋化成工業株式会社
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Publication of WO2023048214A1 publication Critical patent/WO2023048214A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G01N1/12—Dippers; Dredgers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00—Details not covered by any other group of this subclass

Definitions

  • the present invention relates to a sampling sheet, an inspection sheet, and a sample collection method.
  • biomarkers when biomarkers are measured by the above methods, it takes time from sample collection to analysis, and it is difficult to quickly confirm the state of the living body.
  • the apparatus for analyzing biomarkers since the apparatus for analyzing biomarkers is large, it is difficult to install it in an emergency site, an operating room, or the like, where space is limited.
  • this device since this device requires piping for the cleaning liquid and the waste liquid, it is installed fixedly at a predetermined location, making it extremely difficult to move or carry it to a patient at home or to the bedside.
  • Patent Literature 1 discloses a small-sized, portable, and easy-to-handle test sheet that enables rapid processing from sample collection to sample collection. That is, in Patent Document 1, a sheet-like paper substrate having swelling property due to water absorption, a first liquid-resistant film provided on the surface of the paper substrate, and the first liquid-resistant film a second liquid-resistant film that seals from the upper surface a concave-shaped flow path formed on the surface of the paper substrate provided, and a liquid sample is introduced to one end of the flow path.
  • An opening is provided, an air opening is provided at the other end, a sampling channel having a predetermined volume is provided between them, and the first liquid-resistant film and the second liquid-resistant film are provided with At least one of a first capillary force and a first pump pressure driven by expansion of the paper base material due to water absorption through the provided opening causes the liquid sample introduced into the opening to flow through the sampling channel.
  • a first flow path provided with a liquid feeding section for sending to the At least one of a second capillary force and a second pump pressure driven by expansion of the paper substrate due to water absorption through openings provided in the liquid-resistant film and the second liquid-resistant film, and a second flow path provided with a liquid feeding section that feeds the sample sent to the sampling flow path downstream, and is used for mixing the sent sample and a liquid reagent.
  • a test sheet is disclosed in which a cell and a detection cell for detecting characteristics of the sample mixed with the reagent in the mixing cell are formed.
  • Patent Document 1 has the problem that although one-time analysis can be performed quickly, continuous analysis cannot be performed.
  • the present invention is an invention made in view of the above problems, and an object of the present invention is to provide a test sheet that is small, portable, and capable of continuously analyzing samples.
  • An object of the present invention is to provide a sampling sheet, an inspection sheet containing these sheets, and a method for collecting a sample.
  • the present invention includes a sample suction layer, a microneedle formation surface on which sample collection microneedles are formed, and a microneedle layer having an adhesive surface facing the microneedle formation surface and in contact with the sample suction layer.
  • the sample suction layer comprises a first film having a concave channel, and a second film laminated on the first film so as to cover the channel
  • the channel includes a sample channel and a capillary pump connected to the sample channel, and the sample channel is formed with a sample inlet and a driving liquid inlet having a sealing function
  • the driving liquid introduction portion is opened to introduce an amount of the driving liquid that reaches the connection portion between the sample flow channel and the capillary pump, and then the When the driving liquid introduction part is closed, the driving liquid moves to the capillary pump due to capillary action, so that the sample flow path becomes in a negative pressure state, and the sample is sucked into the sample flow path in the negative pressure state.
  • the present invention relates to a sample collection method in which the sample channel is moved to a negative pressure state, and the sample is sucked into the negative pressure sample channel and reaches the capillary pump.
  • a sample suction layer for use in a test sheet that is small, portable, and capable of continuously analyzing samples.
  • FIG. 1 is a cross-sectional view schematically showing an example of a cross section perpendicular to the plane direction of the sampling sheet of the present invention.
  • FIG. 2A is a plan view schematically showing an example of the sample suction layer in the sampling sheet of the present invention.
  • FIG. 2B is a cross-sectional view taken along line AA of FIG. 2A.
  • FIG. 3 is a cross-sectional view schematically showing an example of the sample suction layer preparation step in the sample collection method of the present invention.
  • FIG. 4 is a cross-sectional view schematically showing an example of the sample inflow step in the sample collection method of the present invention.
  • FIG. 5 is a plan view schematically showing an example of the driving liquid introducing step in the sampling method of the present invention.
  • FIG. 6A is a plan view schematically showing an example of a sample collection step in the sample collection method of the present invention.
  • FIG. 6B is a plan view schematically showing an example of the sampling process in the sampling method of the present invention.
  • FIG. 6C is a plan view schematically showing an example of the sampling process in the sampling method of the present invention.
  • FIG. 6D is a plan view schematically showing an example of the sampling process in the sampling method of the present invention.
  • FIG. 7A is a plan view schematically showing an example of a capillary pump in which the sample suction layer of the sampling sheet of the present invention is formed with an atmosphere opening portion.
  • FIG. 7A is a plan view schematically showing an example of a capillary pump in which the sample suction layer of the sampling sheet of the present invention is formed with an atmosphere opening portion.
  • FIG. 7B is a plan view schematically showing an example of a capillary pump in which a liquid absorbing portion is formed in the sample suction layer of the sampling sheet of the present invention.
  • FIG. 8 is a plan view schematically showing an example of the sampling sheet of the present invention having sensor connections.
  • FIG. 9 is a cross-sectional view schematically showing an example of a cross section perpendicular to the planar direction of the inspection sheet of the present invention.
  • FIG. 10 is a schematic diagram schematically showing the transpiration test.
  • the sampling sheet of the present invention includes a sample suction layer, a microneedle formation surface on which sample collection microneedles are formed, and a microneedle having an adhesive surface facing the microneedle formation surface and in contact with the sample suction layer.
  • the sample suction layer includes a first film having a concave channel and a second film laminated on the first film so as to cover the channel.
  • the flow path includes a sample flow path and a capillary pump connected to the sample flow path, and the sample flow path is formed with a sample inflow portion and a driving liquid introduction portion having a sealing function.
  • the driving liquid introduction portion is opened to introduce an amount of the driving liquid that reaches the connection portion between the sample flow channel and the capillary pump, and then When the driving liquid introduction part is closed, the driving liquid moves to the capillary pump due to capillary action, so that the sample flow path becomes in a negative pressure state, and the sample is sucked into the sample flow path in the negative pressure state.
  • the capillary pump can be reached, and the sample-collecting microneedle communicates with the sample inflow portion of the sample suction layer.
  • sampling sheet of the present invention may have any other structure as long as the effect of the invention is exhibited.
  • FIG. 1 is a cross-sectional view schematically showing an example of a cross section perpendicular to the plane direction of the sampling sheet of the present invention.
  • the sampling sheet 2 shown in FIG. 1 faces the sample suction layer 1, the microneedle formation surface 71 on which the sample collection microneedles 80 are formed, and the microneedle formation surface 71, and contacts the sample suction layer 1. and a microneedle layer 70 having an adhesive surface 72 .
  • microneedle layer 70 will be described.
  • the material of the microneedle layer 70 is not particularly limited, for example, metals such as aluminum and stainless alloys, various inorganic materials such as silicon, carbon, ceramics, various mineral materials including calcium-based minerals, and organic polymer compounds. Preferably.
  • the thickness of the microneedle layer is preferably 200 to 3000 ⁇ m, more preferably 500 to 1000 ⁇ m.
  • the sample-collecting microneedle 80 is hollow so that the sample can pass through it.
  • the sample-collecting microneedle 80 communicates with the sample inflow portion 31 of the sample suction layer 1, which will be described later.
  • the material of the sample-collecting microneedle 80 is not particularly limited, but for example, various inorganic materials such as metals such as aluminum and stainless alloys, silicon, carbon, ceramics, various mineral materials including calcium-based minerals, and organic high-strength materials. It is preferably a molecular compound or the like.
  • polystyrene resin examples include polyethylene terephthalate, polyethylene, polypropylene, acrylic resin, epoxy resin, and polystyrene, as well as bioabsorbable polymers.
  • PET polyethylene terephthalate
  • polyethylene polyethylene
  • polypropylene polypropylene
  • acrylic resin epoxy resin
  • polystyrene polystyrene
  • bioabsorbable polymers can be used.
  • ester compounds such as polylactic acid, polyglycolic acid, poly- ⁇ -caprolactone, poly- ⁇ -dioxane, and polymalic acid
  • acid anhydrides such as polyanhydrides
  • orthoester compounds such as polyorthoesters
  • carbonates such as polycarbonates.
  • phosphazene compounds such as polydiaminophosphazene
  • peptide compounds such as synthetic polypeptides
  • phosphate ester compounds such as polyphosphoester urethane
  • carbon-carbon compounds such as polycyanoacrylate, poly- ⁇ -hydroxybutyric acid, polymalic acid, etc.
  • cellulose compounds ethyl cellulose, carboxymethyl
  • the outer diameter of the sample-collecting microneedle 80 is preferably 100-1000 ⁇ m, more preferably 300-700 ⁇ m.
  • the inner diameter of the sample-collecting microneedle 80 is preferably 10 to 100 ⁇ m, more preferably 30 to 70 ⁇ m.
  • the length of the sample-collecting microneedle 80 (distance indicated by symbol L in FIG. 1) is preferably 200 to 2000 ⁇ m, more preferably 500 to 1000 ⁇ m.
  • Only one sample-collecting microneedle 80 may be formed, or a plurality of sample-collecting microneedles 80 may be formed.
  • sample-collecting microneedles 80 are integrally formed with the microneedle layer 70 in FIG. 1, they may be formed as separate members. In this case, the materials of the microneedle layer and the sampling microneedles may be the same or different.
  • the microneedle forming surface 71 may be coated with a hypoallergenic skin adhesive (adhesive composition described in JP-A-2008-247820, etc.) or the like.
  • the microneedle layer can be manufactured by a known method (such as a method using a mold).
  • FIG. 2A is a plan view schematically showing an example of the sample suction layer in the sampling sheet of the present invention.
  • FIG. 2B is a cross-sectional view taken along line AA of FIG. 2A.
  • the sample suction layer 1 shown in FIGS. 2A and 2B comprises a first film 11 having a concave channel 20 and a second film 12 laminated on the first film 11 so as to cover the channel 20. Prepare.
  • the channel 20 includes a sample channel 30 and a capillary pump 40 connected to the sample channel 30.
  • the sample channel 30 includes a sample inlet 31 and a driving liquid inlet 32 having a sealing function. is formed.
  • the drive liquid introduction portion 32 in a state in which the sample can flow into the sample inflow portion 31, the drive liquid introduction portion 32 is opened, and the sample suction layer 1 has an amount that reaches the connection portion 21 between the sample flow path 30 and the capillary pump 40.
  • the driving liquid is introduced and then the driving liquid introduction part 32 is closed, the driving liquid moves to the capillary pump 40 due to capillary action, and the sample channel 30 is put in a negative pressure state. It has the function of being able to reach the capillary pump 40 by being sucked into the channel 30 .
  • the sample collection method of the present invention can be performed using the sampling sheet of the present invention having such functions.
  • the sample collection method of the present invention includes (0) a sample suction layer preparation step, (1) a sample inflow step, (2) a driving liquid introduction step, and (3) a sample collection step. Each step will be described below with reference to the drawings.
  • FIG. 3 is a cross-sectional view schematically showing an example of the sample-absorption layer preparation step in the sample-collecting method of the present invention.
  • a sampling sheet 2 having a sample suction layer 1 is prepared.
  • FIG. 4 is a sectional view schematically showing an example of the sample inflow step in the sample collection method of the present invention.
  • the state in which the sample can flow into the sample inlet of the sample suction layer means the state in which the sample can flow into the sample inlet 31 when the sample is sucked from the sample channel 30. It is not to actively flow the sample into the sample inlet 31 using a pump or the like.
  • the sample 50 can be flowed into the sample flow-in part 31 by the microneedle-derived capillary force, the pressure from the sample 50 side (pressure of body fluid, etc.), or the like. can be done.
  • FIG. 5 is a plan view schematically showing an example of the driving liquid introducing step in the sampling method of the present invention.
  • the driving liquid 60 may reach the connecting portion 21 by capillary force. Further, the drive liquid 60 may reach the connection portion 21 by contracting the volume of the flow path up to the connection portion 21 by deformation due to an external force.
  • the driving liquid 60 has a water-absorbing member (such as a member containing a water-absorbing resin described in Japanese Patent No. 5685007, etc.) at the driving liquid introduction portion, and the water-absorbing member expands as it absorbs the driving liquid.
  • the liquid may reach the connecting portion 21 by contracting the volume of the flow path leading to the connecting portion 21 .
  • FIGS. 6A to 6D are plan views schematically showing an example of the sampling process in the sampling method of the present invention.
  • the driving liquid 60 reaching the connecting portion 21 between the sample flow path 30 and the capillary pump 40 is sucked by the capillary action of the capillary pump 40 .
  • the driving liquid introduction part 32 is closed, as shown in FIG. 6B, the driving liquid 60 moves to the capillary pump 40 by capillary action, and the sample channel 30 becomes negative pressure.
  • FIG. 6C the sample 50 is sucked into the sample channel 30 in the negative pressure state.
  • the sample 50 reaches the capillary pump 40, the sample 50 is sucked into the capillary pump 40 as shown in FIG. 6D.
  • the arrows in FIGS. 6B to 6D indicate the direction of suction.
  • the sampling method of the present invention it is preferable to continuously collect the sample 50 in the sampling step, more preferably to perform the sampling step continuously for 1 to 30 days, and to collect the sample continuously for 14 to 30 days. It is more preferable to carry out the steps.
  • the sample 50 When the sample 50 is sucked into the capillary pump 40 , the sample 50 continuously flows from the sample inlet 31 due to the capillary force of the capillary pump. Therefore, a new sample 50 always flows to one point of the sample channel 30 . Therefore, by analyzing the sample 50 at that one point, the condition of the source of the sample can be monitored over time.
  • First film and second film Materials for the first film and the second film are not particularly limited, but preferably a liquid-resistant film, more preferably a resin film, a paper base film, or the like.
  • the resin film is preferably made of polyolefin, polyurethane, or the like.
  • the paper base film is preferably made of cellulose or the like.
  • the surface of the paper-based film is preferably coated with a waterproof sheet, a hydrophobizing agent, an antiblocking agent, or the like.
  • the first film and the second film may be made of the same material or may be made of different materials.
  • the thickness of the first film is preferably 100-1000 ⁇ m.
  • the thickness of the second film is preferably 1-50 ⁇ m.
  • the flow path is formed in the first film, and the second film is laminated on the first film. If the first film and the second film are laminated so that air does not enter the sample channel from the outside when the sample channel of the channel is in a negative pressure state, the lamination method is not particularly limited. Instead, for example, they may be connected with an adhesive, or they may be connected by thermocompression bonding.
  • a capillary pump has a function of moving a driving liquid and a sample into the capillary pump by capillary action.
  • the shape of the capillary pump in the sampling sheet of the present invention is not particularly limited as long as the driving liquid and the sample can be continuously sucked from the sample channel.
  • the capillary pump 40 may be formed by assembling a plurality of capillaries, as shown in FIG.
  • the capillary force may be exerted by gradually decreasing the cross-sectional area of the capillaries from the inlet of the capillary pump toward the back. Also, the capillary force may be exhibited by changing the material of the inner surface of the capillary so that the wettability of the surface increases as it goes deeper.
  • the inner diameter of the capillary is preferably 20 to 500 ⁇ m, more preferably 40 to 200 ⁇ m.
  • the length of the capillary tube is preferably 4 to 100 mm, more preferably 10 to 50 mm.
  • the number of capillaries is preferably 2-30, more preferably 5-10.
  • the capillary pump has an end connected to the sample channel and an end not connected to the sample channel, and the end not connected to the sample channel of the capillary pump has , an atmosphere opening portion and/or a liquid absorption portion are preferably formed.
  • FIG. 7A is a plan view schematically showing an example of a capillary pump in which the sample suction layer of the sampling sheet of the present invention is formed with an atmosphere opening portion.
  • FIG. 7B is a plan view schematically showing an example of a capillary pump in which a liquid absorbing portion is formed in the sample suction layer of the sampling sheet of the present invention.
  • the capillary pump 40 shown in FIG. 7A has an end portion 41 connected to the sample flow channel 30 and an end portion 42 not connected to the sample flow channel 30. is formed with an air release portion 43 .
  • the atmosphere opening portion 43 means that the capillary pump 40 communicates with the outside air without closing the ends of the capillaries constituting the capillary pump 40 .
  • the driving liquid 60 and the sample 50 that have moved inside the capillary pump 40 reach the atmosphere opening portion 43 .
  • Volatile components in the driving liquid 60 and the sample 50 evaporate from the atmosphere opening portion 43 . Therefore, the capillary pump 40 can constantly exert capillary force.
  • the driving liquid 60 and the sample 50 that have moved in the capillary pump 40 flow out from the end portion 42 that is not connected to the sample channel 30 at a liquid volume of 0.01 to 1 ⁇ L/min per unit time.
  • the volatile components of the driving liquid 60 and the sample 50 that have flowed out as described above evaporate from the atmosphere opening portion 43, but the amount of evaporation per unit time is equal to or greater than the amount of liquid that flows out per unit time. preferable.
  • the amount of liquid flowing out per unit time can be adjusted to a preferable range by adjusting the inner diameter of the sample-collecting microneedle 80 (for example, the amount of liquid flowing out per unit time is 1 ⁇ L/ If it exceeds min, there is a tendency that the amount of liquid flowing out per unit time can be reduced by reducing the inner diameter of the sample-collecting microneedle 80).
  • the capillary pump 40 shown in FIG. 7B has an end portion 41 connected to the sample channel 30 and an end portion 42 not connected to the sample channel 30. , a liquid absorbing portion 44 is formed.
  • the capillary pump 40 has the liquid absorbing section 44 , the driving liquid 60 and the sample 50 that have moved inside the capillary pump 40 reach the liquid absorbing section 44 . Liquid components of the driving liquid 60 and the sample 50 are absorbed by the liquid absorbing section 44 . Therefore, the capillary pump 40 can constantly exert capillary force.
  • the configuration of the liquid absorbing portion is not particularly limited as long as it can absorb liquid, but it is preferable that a water absorbing polymer, quick-drying fiber, or hydrophilic particles are dispersed.
  • the water-absorbing polymer is preferably composed of crosslinked polyacrylic acid sodium salt (water-absorbing resin described in Japanese Patent No. 5685007, etc.).
  • the quick-drying fibers are preferably made of quick-drying fibers such as polyester, cotton, rayon, and cupra. Examples of hydrophilic particles include colloidal silica and diatomaceous earth compounds (bentonite, etc.).
  • the quick-drying fiber from the viewpoint of long-term continuous use, the following test was carried out, and the "time until the residual water content became 10% by weight or less" is preferably a fiber of 145 min or less, and 100 min or less. is more preferred, and fibers with 90 min or less are particularly preferred.
  • ⁇ Evaluation test of quick-drying fiber> The quick-drying fiber is cut into a size of 100 mm ⁇ 100 mm to obtain a quick-drying fiber test piece. Next, the quick-drying fiber test piece is brought into contact with a 100 mm ⁇ 100 mm filter paper (circular quantitative filter paper No.
  • hydrophilic particles from the viewpoint of long-term continuous use, the following test was carried out, and "the time until the residual water content became 10% by weight or less" is preferably particles of 145 minutes or less, and 100 minutes or less. is more preferred, and particles with 90 min or less are particularly preferred.
  • Hydrophilic particles are dispersed in water to prepare a 30% by weight aqueous dispersion of hydrophilic particles.
  • a 100 mm ⁇ 100 mm filter paper (circular quantitative filter paper No. 5C) is impregnated with 1 mL of a 30% by weight aqueous dispersion of hydrophilic particles, and dried with a circulating air dryer under the conditions of 130 ° C. for 30 minutes.
  • sample flow path The sample channel is not particularly limited as long as the drive liquid and the sample can pass through it, but the width is preferably 20 to 500 ⁇ m, more preferably 4 to 200 ⁇ m.
  • Only one sample inlet portion may be formed in the sample channel, or a plurality of sample inlet portions may be formed.
  • the method of using the microneedles is mentioned as a means for inflowing the sample into the sample inflow part.
  • the driving liquid introduction part has a sealing function.
  • the driving liquid introduction part has a shape that allows the driving liquid to be introduced into the sample channel.
  • the "sealing function" means a function that can seal the driving liquid introduction part to such an extent that air does not flow in from the driving liquid introduction part when the sample channel is in a negative pressure state.
  • the driving liquid introduction section may have a pumping function for causing the driving liquid to reach the connecting section between the sample channel and the capillary pump.
  • the driving liquid introduction section is formed between the sample inflow section and the connection section. It should be noted that only one drive liquid introduction portion may be formed, or a plurality of drive liquid introduction portions may be formed.
  • Examples of the sealing function of the driving liquid introduction section include a function of sealing the driving liquid introduction section with a manual valve or an electric valve. Further, it may have a function of being deformed by an external force to seal the driving liquid introducing portion. Furthermore, the function may be such that the driving liquid introduction section has a water absorbing member, and the water absorbing member absorbs the driving liquid and expands to seal the driving liquid introduction section.
  • aspects such as the shape of the capillary pump and the sample flow channel are selected so that the sample suction layer of the sampling sheet of the present invention can exhibit its function. It is preferable to set appropriately according to the type.
  • FIG. 8 is a plan view schematically showing an example of the sampling sheet of the present invention having sensor connections.
  • the sample suction layer 1 shown in FIG. 8 has a sensor connection portion 33 formed in the sample channel 30 .
  • the sensor connecting portion 33 is not particularly limited in position as long as it is formed in the sample channel 30 . may be By connecting a sensor to the sensor connection portion 33, the sample 50 flowing through the sample channel 30 can be analyzed by the sensor.
  • the sample suction layer in the sampling sheet of the present invention can continuously suck the sample, it is possible to continuously monitor the state of the source of the sample.
  • the driving liquid used when collecting a sample using the sample suction layer in the sampling sheet of the present invention is water, physiological saline, or the like. Among these, physiological saline is more preferable.
  • the source of the sample collected using the sample suction layer in the sampling sheet of the present invention is preferably a living body such as a human.
  • the sample to be collected is preferably body fluid such as interstitial fluid and blood.
  • interstitial fluid is more preferable.
  • the interstitial fluid has a low solids content and a low non-volatile content. Therefore, when interstitial fluid is used as a sample, the channel is less likely to be clogged with solids and deposited non-volatile components.
  • the sample channel 30 has a single tubular structure, and the sample inflow portion 31 and the driving liquid introduction portion 32 are formed one each.
  • the sample channel may be branched or may be plural.
  • the sample channel may be formed in a straight line, curved line, or curved line. Also, a plurality of sample inlets and drive liquid inlets may be formed.
  • the capillary pump 40 is formed at one location, but the sample suction layer of the sampling sheet of the present invention may have capillary pumps formed at a plurality of locations.
  • Base film preparation step A paper base film is prepared as a base film. After that, the surface forming the flow path is waterproofed.
  • Methods of waterproofing include a method of attaching a waterproof sheet to the base film and a method of applying a hydrophobizing agent to the surface of the base film.
  • Second film lamination step Next, a second film is laminated on the surface of the first film on which the flow paths are formed.
  • the first film and the second film can be laminated by an ordinary method such as an adhesive agent or thermocompression bonding.
  • the sample suction layer of the sampling sheet of the present invention can be manufactured.
  • the first film having the flow path may be manufactured by a resin molding method such as a 3D printer.
  • FIG. 9 is a cross-sectional view schematically showing an example of a cross section perpendicular to the planar direction of the inspection sheet of the present invention.
  • the inspection sheet 3 shown in FIG. 9 is composed of the sampling sheet 2 and a sensing layer 90 laminated on the sample suction layer 1 of the sampling sheet 2 and having a sensor 91 .
  • the sensor connection portion 33 is formed in at least a part of the sample channel 30 of the sample suction layer 1 , and the sensor 91 of the sensing layer 90 is connected to the sensor connection portion 33 of the sample suction layer 1 . It is connected to the.
  • samples in the living body can be continuously collected. Therefore, by analyzing the sample with the sensor 91, the biological biomarkers can be continuously monitored, and the biological information can be confirmed in real time.
  • the biomarkers to be analyzed by the sensor 91 are preferably set appropriately according to the purpose, and may be low-molecular-weight biomarkers such as cortisol and blood sugar, or high-molecular-weight biomarkers such as proteins and nucleic acids. Also, the sensor 91 may be used to analyze pH and odor components.
  • the sensing layer 90 and the sampling sheet 2 can be separated, and the sampling sheet 2 may be disposable. With such a structure, it is possible to repeatedly use the inspection sheet 3 by exchanging the sampling sheet 2 .
  • the inspection sheet 3 may have a communication device that enables communication between the sensor 91 and an external recording device or control device. If the inspection sheet 3 has such a communication device, it is possible to easily monitor the living body and control the sensor 91 .
  • the inspection sheet 3 may have a pseudo skin layer as the outermost layer.
  • the pseudo-skin layer is composed of a pseudo-skin positioned outside and an elastic layer formed inside the pseudo-skin.
  • the artificial skin is preferably made of urethane skin agent, synthetic rubber (such as silicone rubber), natural rubber, or the like.
  • the elastic layer is preferably made of urethane protective layer, polystyrene foam, polymer sponge, or the like. If the test sheet 3 has a pseudo skin layer, the sensing layer 90 and the sampling sheet 2 can be protected against external impact. In addition, the appearance of the inspection sheet 3 can be made to resemble the skin of a living body.
  • the present disclosure (1) includes a sample suction layer, a microneedle formation surface on which sample collection microneedles are formed, and a microneedle having an adhesive surface facing the microneedle formation surface and in contact with the sample suction layer.
  • the sample suction layer includes a first film having a concave channel and a second film laminated on the first film so as to cover the channel.
  • the flow path includes a sample flow path and a capillary pump connected to the sample flow path, and the sample flow path is formed with a sample inflow portion and a driving liquid introduction portion having a sealing function.
  • the driving liquid introduction portion is opened to introduce an amount of the driving liquid that reaches the connection portion between the sample flow channel and the capillary pump, and then When the driving liquid introduction part is closed, the driving liquid moves to the capillary pump due to capillary action, so that the sample flow path becomes in a negative pressure state, and the sample is sucked into the sample flow path in the negative pressure state.
  • the microneedle for sample collection is a sampling sheet communicating with the sample inflow portion of the sample suction layer.
  • the present disclosure (2) is the sampling sheet according to the present disclosure (1), wherein the driving liquid introduction section is formed between the sample inflow section and the connection section.
  • the capillary pump has an end connected to the sample channel and an end not connected to the sample channel, and the end of the capillary pump not connected to the sample channel is the sampling sheet according to (1) or (2) of the present disclosure, in which an atmosphere opening portion and/or a liquid absorbing portion are formed.
  • the present disclosure (4) is the sampling sheet according to the present disclosure (3), wherein the liquid absorbing portion is dispersed with a water absorbing polymer.
  • the present disclosure (5) is the sampling sheet according to any one of the present disclosures (1) to (4), wherein a sensor connection portion is formed in at least a part of the sample channel.
  • the present disclosure (6) comprises the sampling sheet according to the present disclosure (5), and a sensing layer laminated on the sample suction layer of the sampling sheet and having a sensor, wherein the sensor of the sensing layer includes the sample A test sheet connected to the sensor connection portion of the suction layer.
  • the present disclosure (7) uses the sample-collecting microneedle constituting the sampling sheet according to any one of the present disclosure (1) to (5) to allow a sample to flow into the sample inflow portion of the sample suction layer.
  • the driving liquid introduction part is closed, and the driving liquid is moved to the capillary pump by capillary action to put the sample channel in a negative pressure state, and the sample is sucked into the sample channel in the negative pressure state, and the capillary is moved. and a sampling step of reaching the pump.
  • the present disclosure (8) is the sampling method according to the present disclosure (7), in which the samples are continuously collected in the sample collection step.
  • the present disclosure (9) is the sampling method according to the present disclosure (7) or (8), wherein the sampling step is performed continuously for 1 to 30 days.
  • the present disclosure (10) is the sampling method according to any one of the present disclosure (7) to (9), wherein the sample is interstitial fluid.
  • Quick-drying fibers Dry-X (manufactured by Daiichi Boseki Co., Ltd.) and Powered Spun (manufactured by Fine Track Co., Ltd.) were prepared and cut into a size of 100 mm ⁇ 100 mm to obtain a quick-drying fiber test piece. .
  • the time required for the residual water content of the filter paper to reach 10% by weight or less was measured.
  • the quick-drying fiber used is dry-ex, it takes 70 minutes to reach 10% by weight or less.
  • the quick-drying fiber used was a powered spun, it took 75 minutes to reach 10% by weight or less.
  • hydrophilic particles As hydrophilic particles, SNOWTEX 30 (manufactured by Nissan Chemical Co., Ltd.) was dispersed in water to prepare an aqueous dispersion of 30% by weight of hydrophilic particles. Next, a 100 mm ⁇ 100 mm filter paper (circular quantitative filter paper No. 5C) was impregnated with 1 mL of a 30% by weight aqueous dispersion of Snowtex 30, and dried at 130 ° C. for 30 minutes with a circulation dryer. A hydrophilic particle specimen was prepared that was dried and impregnated with hydrophilic particles.
  • a filter paper (circular quantitative filter paper No. 5C) was cut into a size of 10 mm ⁇ 10 mm to obtain a test sample 1. Dry-ex and filter paper (circular quantitative filter paper No. 5C) were cut into pieces of 10 mm ⁇ 10 mm, and these were superimposed to obtain test sample 2. A powered span and filter paper (circular quantitative filter paper No. 5C) were cut into 10 mm ⁇ 10 mm pieces, and these were superimposed to obtain test sample 3. An aqueous dispersion of 3% by weight Snowtex 30 was prepared. Next, filter paper (circular quantitative filter paper No.
  • FIG. 10 is a schematic diagram schematically showing the transpiration test.
  • a capillary 140 was prepared and positioned such that one end 142 of capillary 140 contacted each test sample 144 .
  • 0.5 ⁇ L of water was intermittently added from the other end 141 of the capillary 140 once every 10 minutes. This operation reproduced the state in which the amount of water flowing out from one end 142 per unit time was 0.05 ⁇ m/min.
  • the weight of water in each test sample was measured 1 hour, 2 hours and 3 hours after the start of water addition.
  • the weight of water contained in each test sample was calculated from the weight of each test sample 1 hour, 2 hours and 3 hours after the start of water addition, and the weight of each test sample when dry (before the start of the test). It was calculated as a numerical value after subtracting the weight. Table 1 shows the results.
  • test samples 2 to 4 showed less increase in weight of water contained in the test samples than test sample 1 over time. This is probably because the test samples 2 to 4 have better moisture transpiration properties than the test sample 1.
  • the use of Dry-X, Powered Spun, and Snowtex 30 as the material for the liquid-absorbing portion improves the transpiration of water. Therefore, it is considered that a sampling sheet having a liquid absorbing portion using these materials can be used continuously for a long period of time.
  • the sampling sheet of the present invention By using the sampling sheet of the present invention, it is possible to continuously aspirate samples. Therefore, the sampling sheet of the present invention is useful as a configuration for successively aspirating a sample in a test sheet for successively and instantaneously monitoring biological information.

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  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Hydrology & Water Resources (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

L'invention concerne une feuille d'échantillonnage, petite et portative, destinée à être utilisée comme feuille d'inspection et permettant d'analyser successivement des échantillons. La feuille d'échantillonnage selon la présente invention comprend une couche d'aspiration d'échantillon et une couche de microaiguilles dotée d'une surface de formation de microaiguilles sur laquelle sont formées des microaiguilles collectrices d'échantillons et une surface adhésive faisant face à la surface de formation de microaiguilles et en contact avec la couche d'aspiration d'échantillon, la couche d'aspiration d'échantillon comportant un premier film présentant un trajet d'écoulement en creux et un second film stratifié sur le premier film de manière à couvrir le trajet d'écoulement, le trajet d'écoulement comportant un trajet d'écoulement d'échantillon et une pompe capillaire raccordée au trajet d'écoulement d'échantillon, une partie d'entrée d'échantillon et une partie d'introduction de liquide d'entraînement ayant une fonction d'étanchéité étant formées dans le trajet d'écoulement d'échantillon, dans un état dans lequel l'échantillon peut s'écouler dans la partie d'entrée d'échantillon, la partie d'introduction de liquide d'entraînement est ouverte pour introduire un liquide d'entraînement en une quantité qui atteint une partie de raccordement entre le trajet d'écoulement d'échantillon et la pompe capillaire, et lorsque la partie d'introduction de liquide d'entraînement est ensuite fermée, le liquide d'entraînement se déplace vers la pompe capillaire sous l'effet de l'action capillaire, de sorte que le trajet d'écoulement de l'échantillon se trouve dans un état de pression négative, l'échantillon est aspiré dans le trajet d'écoulement de l'échantillon dans l'état de pression négative, de sorte que la pompe capillaire peut être atteinte, et les microaiguilles collectrices d'échantillon communiquent avec la partie d'entrée d'échantillon de la couche d'aspiration d'échantillon.
PCT/JP2022/035338 2021-09-24 2022-09-22 Feuille d'échantillonnage, feuille d'inspection et procédé de collecte d'échantillon WO2023048214A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5688635B2 (ja) * 2010-08-26 2015-03-25 国立大学法人 東京大学 検査用シート、化学分析装置及び検査用シートの製造方法
WO2019176126A1 (fr) * 2018-03-16 2019-09-19 国立大学法人東京大学 Puce d'inspection et dispositif d'inspection
JP2021506391A (ja) * 2017-12-22 2021-02-22 ブリテル アクチエボラグ パブリークＢｒｉｇｈｔｅｒ Ａｂ （Ｐｕｂｌ） 診断用皮膚パッチ

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5688635B2 (ja) * 2010-08-26 2015-03-25 国立大学法人 東京大学 検査用シート、化学分析装置及び検査用シートの製造方法
JP2021506391A (ja) * 2017-12-22 2021-02-22 ブリテル アクチエボラグ パブリークＢｒｉｇｈｔｅｒ Ａｂ （Ｐｕｂｌ） 診断用皮膚パッチ
WO2019176126A1 (fr) * 2018-03-16 2019-09-19 国立大学法人東京大学 Puce d'inspection et dispositif d'inspection

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