WO2022208321A1 - Dispositif de diagnostic incurvé - Google Patents

Dispositif de diagnostic incurvé Download PDF

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Publication number
WO2022208321A1
WO2022208321A1 PCT/IB2022/052855 IB2022052855W WO2022208321A1 WO 2022208321 A1 WO2022208321 A1 WO 2022208321A1 IB 2022052855 W IB2022052855 W IB 2022052855W WO 2022208321 A1 WO2022208321 A1 WO 2022208321A1
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WO
WIPO (PCT)
Prior art keywords
substrate
curved
diagnostic device
plane
porous substrate
Prior art date
Application number
PCT/IB2022/052855
Other languages
English (en)
Inventor
Matthew S. Stay
Daniel J. Theis
Mikhail L. Pekurovsky
Ronald P. Swanson
Original Assignee
3M Innovative Properties Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 3M Innovative Properties Company filed Critical 3M Innovative Properties Company
Publication of WO2022208321A1 publication Critical patent/WO2022208321A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54386—Analytical elements
    • G01N33/54387—Immunochromatographic test strips
    • G01N33/54391—Immunochromatographic test strips based on vertical flow
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5023—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/126—Paper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces

Definitions

  • CURVED DIAGNOSTIC DEVICE BACKGROUND Simple, low-cost diagnostic technologies are an important component of strategies for improving healthcare and access to healthcare in developing nations and resource-limited settings.
  • Inexpensive, portable, and easy-to-use diagnostic devices have used a porous substrate including a reagent selected to rapidly perform quantitative or qualitative analysis of a fluid sample such as, for example, a bodily fluid, an industrial fluid, or water, in the field when laboratory facilities are not available or easily accessed for sample analysis.
  • a paper-based diagnostic device includes a colorimetric immunoassay reagent with a color change as a readout, and the color change readout can be detected visually or with a machine to provide a rapid, low-cost diagnosis of the presence of an infectious disease.
  • analytes in a sample can be rapidly detected using the diagnostic devices include viral antigens, bacterial antigens, fungal antigens, parasitic antigens, cancer antigens, metabolic markers, and combinations thereof.
  • antibodies acting as binding proteins can be used to capture disease-relevant biomarkers from the patient sample, and then produce a visible diagnostic signal resulting from the binding event.
  • a diagnostics device including an elongate porous substrate.
  • the substrate includes a first portion in a first plane and a second portion in a second plane substantially parallel to the first plane. The first portion overlies the second portion.
  • the first portion includes a first hydrophilic region
  • the second portion includes a second hydrophilic region
  • the first and second hydrophilic regions are aligned to provide a sample flow path between the first portion of the substrate and the second portion of the substrate along a direction substantially normal to the first plane and the second plane.
  • a curling mechanism includes a curved surface.
  • the elongated porous substrate is laminated on the curved surface, and the elongate porous substrate is in a curved state to create a tension to press the first portion and the second portion together.
  • the present disclosure describes a method of making a diagnostic device.
  • the method includes providing an elongate, substantially planar porous substrate including a first portion in a first plane and a second portion in a second plane substantially parallel to the first plane.
  • the first portion overlies the second portion, the first portion includes a first hydrophilic region, the second portion includes a second hydrophilic region, and the first and second hydrophilic regions are aligned to provide a sample flow path between the first portion of the substrate and the second portion of the substrate along a direction substantially normal to the first plane and the second plane.
  • the method further includes laminating the elongated porous substrate on a curved surface of a curling mechanism such that the elongated porous substrate is in a curved state to create a tension to press the first portion and the second portion together.
  • FIG.1A is schematic cross-sectional view of an embodiment of a portion of a diagnostic device according to the present disclosure.
  • FIG.1B is schematic cross-sectional view of another embodiment of a portion of a diagnostic device according to the present disclosure.
  • FIG.2A is schematic diagram of a process to apply an elongate porous layered substrate to a curved surface, according to one embodiment of the present disclosure.
  • FIG.2B is a schematic cross-sectional view of an embodiment of a diagnostic device according to the present disclosure.
  • FIG.3 is a schematic cross-sectional view of another embodiment of a diagnostic device according to the present disclosure.
  • FIG.4 is a schematic cross-sectional view of another embodiment of a diagnostic device according to the present disclosure.
  • FIG.5 is a schematic cross-sectional view of another embodiment of a diagnostic device according to the present disclosure.
  • FIG.6 is a schematic cross-sectional view of another embodiment of a diagnostic device according to the present disclosure.
  • FIG.7 is a schematic diagram of a pattern of hydrophobic ink for the Curved Device Example.
  • FIG.8 is an optical image of the Curved Device Example.
  • FIG.9 is an optical image of the unfolded paper device and blotting pad after separation for the Curved Device Example.
  • FIG.10 is an optical image of a paper-based device.
  • FIG.11 is an optical image of the unfolded paper device and blotting pad after separation for the Comparative Example.
  • like reference numerals indicate like elements. While the above-identified drawing, which may not be drawn to scale, sets forth various embodiments of the present disclosure, other embodiments are also contemplated, as noted in the Detailed Description.
  • a viscosity of “about” 1 Pa-sec refers to a viscosity from 0.95 to 1.05 Pa-sec, but also expressly includes a viscosity of exactly 1 Pa-sec.
  • a perimeter that is “substantially square” is intended to describe a geometric shape having four lateral edges in which each lateral edge has a length which is from 95% to 105% of the length of any other lateral edge, but which also includes a geometric shape in which each lateral edge has exactly the same length.
  • the term “substantially” with reference to a property or characteristic means that the property or characteristic is exhibited to a greater extent than the opposite of that property or characteristic is exhibited.
  • a substrate that is “substantially” transparent refers to a substrate that transmits more radiation (e.g. visible light) than it fails to transmit (e.g. absorbs and reflects).
  • a substrate that transmits more than 50% of the visible light incident upon its surface is substantially transparent, but a substrate that transmits 50% or less of the visible light incident upon its surface is not substantially transparent.
  • the singular forms “a”, “an”, and “the” include plural referents unless the content clearly dictates otherwise.
  • reference to fine fibers containing “a compound” includes a mixture of two or more compounds.
  • FIG.1A is schematic cross-sectional view of an embodiment of a portion of a diagnostic device 100 according to the present disclosure.
  • the diagnostic device 100 includes an elongated substantially planar porous substrate 10 extending along a longitudinal direction (e.g., the x axis in FIG.1A) between a first end 11 and a second end 13 thereof.
  • the substrate 10 includes a first sheet-like portion 12 in a first plane and a second sheet-like portion 14 in a second plane substantially parallel to the first plane.
  • the first sheet-like portion 12 overlies the second sheet-like portion 14.
  • the first sheet-like portion 12 includes a first hydrophilic region 122.
  • the second sheet-like portion 14 includes a second hydrophilic region 142.
  • the first hydrophilic region 122 of the first sheet-like portion 12 and the second hydrophilic region 142 of the second sheet-like portion 14 are aligned to provide a sample flow path as indicated by an arrow a1 between the first portion 12 of the substrate 10 and the second sheet-like portion 14 of the substrate 10 along a direction (e.g., the axis y in FIG.1A) substantially normal to the first plane and the second plane.
  • a1 between the first portion 12 of the substrate 10 and the second sheet-like portion 14 of the substrate 10 along a direction (e.g., the axis y in FIG.1A) substantially normal to the first plane and the second plane.
  • the first and second substrate portions 12, 14 each may include multiple hydrophilic regions which may be aligned to form multiple sample flow paths such as the paths indicated by arrows a1 and a2.
  • the elongate substrate 10 may be formed by folding an elongate substantially planar substrate at one or more folded regions such that the first and second sheet-like portions 12 and 14 are stacked to form a layered structure.
  • the substrate 10 may extend along the z axis.
  • the substrate 10 may be folded along the z direction such that the one or more folded regions are located at the first end 11 and/or the second end 13, extending along the longitudinal direction (e.g., the z axis in FIG.1A) substantially normal to the cross direction (e.g., the x axis in FIG.1A) of the substrate 10.
  • the substrate 10 may elongate along the x axis.
  • the substrate 10 may be folded along the x direction such that the one or more folded regions are located at the first end 11 and/or the second end 13, extending along the cross direction (e.g., the z axis in FIG.1A) substantially normal to the longitudinal direction (e.g., the x axis in FIG.1A) of the substrate 10.
  • the one or more folded regions at the end 11 (13) separate the substrate 10 into the first sheet-like portion 12 and the second sheet-like portion 14, each occupying a substantially parallel plane with respect to the folded regions. It is to be understood that in some embodiments, multiple layers of substrates can be laminated in a manner other than folding to form an elongate substrate.
  • the elongate hydrophilic substrate 10 may be made from any porous, hydrophilic, adsorbent material capable of wicking a sample fluid by capillary action.
  • the substrate 10 is a paper product such as, for example, chromatographic paper, filter paper, and the like, but may also be chosen from woven or nonwoven fabrics, or from polymer films such as, for example, nitrocellulose, cellulose acetate, polyesters, and polyurethane, and the like.
  • Suitable sample fluids include, but are not limited to, body fluids (e.g., blood, sputum, saliva, or urine), industrial fluids, water samples, and the like.
  • the first substrate portion 12 includes a first hydrophobic region 124 adjacent to the first hydrophilic region 122, while the second substrate portion 14 includes a second hydrophobic region 144 adjacent to the second hydrophilic region 142.
  • the first and second hydrophobic regions 124, 144 may be formed by applying a desired pattern of a low surface energy polymeric material such as, for example, a polymeric ink composition, to an elongate hydrophilic substrate.
  • the substrate 10 in the hydrophobic regions 124, 144 have applied thereto a low surface energy polymeric material, and as such resist unassisted capillary fluid flow or wicking of a selected fluid, such as, for example, a sample fluid including, for example, an analyte, or a buffer or a wash solution, therethrough.
  • a selected fluid such as, for example, a sample fluid including, for example, an analyte, or a buffer or a wash solution, therethrough.
  • the selected fluid is passively transported (requiring no external pressure gradients, gravitational or electrostatic forces) between the hydrophilic regions 122, 142.
  • the hydrophobic regions 124, 144 substantially confine the flow of the fluid along the direction of the arrow a1, which is aligned along thickness of the substrate portions 12, 14, or along the y-axis of the three-dimensional diagnostic device 10.
  • the hydrophilic regions 124, 144 are sufficiently aligned with each other such that a fluid sample placed on the first hydrophilic region 122 can be passively transported using, for example, wicking or capillary action, along the sample flow path a1 to provide fluid communication between the first substrate portion 12 and the second substrate portion 14 such that the fluid sample wicks into the second hydrophilic region 142.
  • all or a portion of one or both of the hydrophilic regions 122, 142 can include a test area where an analytical result or output of the device 10 can be displayed for a user, as well as one or more reagents in the test area or in fluid communication with the test area.
  • the reagents are selected to provide an indication of at least one of a presence, absence or concentration of an analyte in the fluid sample that are disposed in the sample flow path a1.
  • the reagents can be applied to all or a portion of one or both of the hydrophilic regions 122, 142, can be in another portion of the device 10 and in fluid communication with the flow path a1, or can be applied to the sample flow path a1 before or after the application of the fluid sample to the sample flow path.
  • Various applications were discussed in U.S. Patent Application No.63/003,169 (Pekurovsky et al., Attorney’s Docket No.82793US002), which is incorporated herein by reference.
  • the first substrate portion 12 includes a first major surface 121 and a second major surface 123
  • the second substrate portion 14 includes a first major surface 141 and a second major surface 143.
  • the first portion of the substrate 12 and the second portion of the substrate 14 overlie one another such that the respective major surfaces 123 and 141 are adjacent to each other.
  • two overlying substrate layers or portions 12, 14 are illustrated in the embodiment of FIG.1A, it is to be understood that the substrate 10 may include more than two overlying layers.
  • Each substrate layer or portion can be stacked on each other and each occupy a different and substantially parallel plane to form a three-dimensional structure.
  • the number of overlying substrate layers or portions may be, for example, in the range from 2 to 8.
  • the diagnostic device 10 may include an optional connective regions including any suitable connection mechanism (e.g., an adhesive layer) disposed between the second major surface 123 of the first substrate portion 12 and the first major surface 141 of the second substrate portion 14.
  • any suitable connection mechanism e.g., an adhesive layer
  • the adjacent major surfaces 123, 141 of the overlying substrate portions 12, 14 can include one or more connective regions, which adhere the first substrate portion 12 to the second substrate portion 14 and maintain the registration of the hydrophilic regions 122, 142 to preserve the sample flow path.
  • the optional connective regions can be disposed, for example, between the adjacent hydrophobic regions such as the hydrophobic region 124, 144.
  • an optional connection mechanism e.g., an adhesive layer
  • an adhesive layer may be disposed adjacent to the end 11 or 13 of the substrate 10 to maintain the mechanical integrity of the device 10.
  • Any suitable connection mechanism can be used, including, for example, adhesive materials, mechanical fasteners, alone or in combination. It is to be understood that when the device 10 is formed by folding a substrate, the folding regions may function as springs that may push the adjacent substrate layers or portions apart. A connection mechanism may be provided to constrain the spring action.
  • FIG.1B is schematic cross-sectional view of an embodiment of a portion of a diagnostic device 100’ according to the present disclosure.
  • the diagnostic device 100’ includes an elongated substantially planar porous substrate 10’ extending along a longitudinal direction (e.g., the x axis in FIG.1A’) between a first end 11’ and a second end 13’ thereof.
  • the substrate 10’ includes a first sheet-like portion 12’ in a first plane and a second sheet-like portion 14’ in a second plane substantially parallel to the first plane.
  • the first sheet-like portion 12’ overlies the second sheet- like portion 14’.
  • the first sheet-like portion 12’ includes a first hydrophilic region 122’.
  • the second sheet-like portion 14 includes a second hydrophilic region 142’.
  • the first hydrophilic region 122’ of the first sheet-like portion 12’ and the second hydrophilic region 142’ of the second sheet-like portion 14 are aligned to provide a sample flow path as indicated by an arrow a1 between the first portion 12’ of the substrate 10’ and the second sheet-like portion 14’ of the substrate 10 along a direction (e.g., the axis y in FIG.1B) substantially normal to the first plane and the second plane.
  • the first substrate portion 12’ further includes a first hydrophobic region 124’ adjacent to the second hydrophilic region 142’ of the second portion such that a second sample flow path within the second hydrophilic region of the second portion along a direction substantially parallel to the second plane.
  • the second sample flow path as indicated by the arrow a2 is fluidly connected to the first sample flow path as indicated by the arrow a1.
  • a gap (e.g., gap 31 in FIG.1A, gap 31’ in FIG.1B) may be formed between the adjacent major surfaces of the overlying substrate portions (e.g., 12, 14 in FIG.1A, 12’, 14’ in FIG.1B).
  • a sample fluid may flow into the gap along a lateral direction, for example, as indicted by an arrow a3 in FIG.1B.
  • the sample liquid flows in the gap 31, 31’ between the layers along the lateral direction, instead of flow in a designed sample fluid flow path, it may not reach and react with reagents deposited in a test area at a hydrophilic region such as the hydrophilic region 142 of the second substrate portion 14.
  • the sample fluid may not connect or bridge between two adjacent hydrophilic regions, and a vertical sample flow path (e.g., the flow paths a1 and a2 in FIG.1A, and the flow path a1 in FIG. 1B.) may not be effectively formed.
  • a connection mechanism e.g., an adhesive layer
  • an adhesive layer between the layers may introduce other challenges, for example, complexity of manufacturing, wicking of adhesive into substrate pores under environmental conditions and prolonged storage, interfering with chemical reactions related to the testing of sample fluid, etc.
  • a curling mechanism is provided to compress the stacked layers tightly against each other to eliminate or mitigate a significant gap between the adjacent substrate layers or portions.
  • a gap is considered significant when the gap is greater than 75 micrometers, greater than 50 micrometers, greater than 25 micrometers, greater than 10 micrometers, greater than 5 micrometers, greater than 2 micrometers, greater than one micrometer, etc.
  • a gap is considered significant when the fraction of fluid sample flowing into the gap is more than 20 weight %, more than 10 weight %, 5 weight %, 2 weight %, 1 weight %, etc.
  • the curling mechanism includes a curved surface.
  • An elongate porous substrate described herein is laminated on the curved surface of the curling mechanism, and the elongated porous substrate is in a curved state to create a tension to press the adjacent substrate layers or portions (e.g., the first substrate portion 12, 12’ and the second substrate portion 14, 14’ in FIGS.1A-B) together to mitigate or eliminate the significant gap 31, 31’ therebetween and exclude the air layer in the gap.
  • the curling mechanism can provide a compression force such that the adjacent substrate layers or portions are in intimate contact, where it mitigates liquid flow between the layers to such a level that device performance (e.g., the ability to detect the antigen of interest) is not impacted in a negative way.
  • a minimum force between the layers is a threshold level that provides the needed intimate contact.
  • the minimum force may be, for example, 0.5 pound-force per square inch (psi) or 3.45 kilopascal.
  • this compression force may decay over time.
  • One approach to avoid this decay is to attach the substrate over the curved surface at the final point of use and avoiding the time dependent decay of the compression force.
  • FIG.2A is schematic diagram of a process to apply the elongate porous substrate 10 of FIG.1 to a curved surface 32, according to one embodiment of the present disclosure.
  • FIG.2B is a schematic cross-sectional view of a diagnostic device 200 formed by assembling the substrate 10 and the curved surface 32.
  • the curved surface 32 may have at least a portion to be substantially convex.
  • the at least one convex surface portion may have a radius of curvature in the range, for example, from 6 to 24 inches (or 15 to 60 cm).
  • a substantially convex surface portion may have a radius of curvature in the range, for example, no less than one inch (25.4 mm), no less than 2 inches, or no less than 3 inches.
  • a curved surface When the substrate is attached to a convex surface, the substrate is in a curved state with an outside convex surface where a sample fluid can be deposited and transport via sample flow paths within the substrate.
  • a curved surface may have various curved shapes as long as when a porous substrate is mounted on the curved surface, the substrate is in a curved state to create a tension to press the adjacent substrate layers together.
  • a curved surface that is substantially convex may have at least a portion with an infinite radius of curvature, in which case it may be considered approximately straight. It is to be understood that a curved surface may not be composed of a purely circular arc, and may have any desired convex- shaped geometries.
  • a curved surface that is substantially convex may include multiple facets having various radius of curvatures.
  • the curved surface 32 can be a major surface of a curved or curled rigid layer made by any suitable material such as, for example, thermo-formed PET.
  • the curved or curled rigid layer may have a thickness in a range, for example, from 10 to 20 mils (0.25 mm to 0.5 mm).
  • the layer providing the curved surface or a curved supporting layer is sufficiently rigid such that in comparison to and combined with the assembly of substrate layers, the bending of the rigid layer can have its neutral axis (i.e., a region of zero stress) approximately near the center of its thickness.
  • the curved layer may have a modulus of elasticity substantially greater (e.g., at least 10 times, 20 times, 30 times, or 50 times greater) than that of the stacked substrate layers.
  • a curved layer and the stacked substrate layers attached thereon can be constructed such that the value of (modulus x cross sectional area) for the stacked substrate layers is substantially less than that for the curved layer.
  • a substantially planar porous substrate including multiple overlying substrate layers can be first disposed on a substantially planar surface of a supporting layer.
  • the supporting layer can be bended to form a curved layer having a convex surface where the substrate is disposed.
  • the substrate 10 can be attached to the curved surface 32 via an adhesive material.
  • a suitable adhesive may include, for example, pressure sensitive adhesives, hot- melt adhesives, cohesive adhesives, and mixtures and combinations thereof.
  • the term cohesive adhesive refers to adhesive materials that adhere to each other, but have low adhesion, or no adhesion, to other non-adhesive surfaces.
  • the adhesive or cohesive bond between the substrate layers or portions can sufficiently bind the substrate layers/portions together such that the shear forces generated when the stack is curved, may not exceed the shear limit between layers.
  • the adhesive or cohesive force can withstand the shear force between the bound substrate layers imposed on those layers when undergoing the process of curving.
  • the adhesive can be disposed between an outer surface of the substrate 10 and the curved surface 32 such that the substrate 10 is conformally attached to the curved surface 32 and the layers 12, 14 of the substrate 10 are held under compression to be in close proximity with each other.
  • the outer surface of the substrate 10 is the outmost surface of the substrate 10, which can be, for example, a major surface of an outer layer of the substrate (e.g., the first major surface 121 of the first substrate portion 12, the second major surface 123 of the second substrate portion 14, an outer surface of the optional layer 16, etc.).
  • one or more connective regions are located adjacent to the first end and the second end of the substrate to maintain the elongated porous substrate in the curved state.
  • the connective regions may include any suitable connection mechanism such as, for example, adhesive materials, mechanical fasteners, alone or in combination to maintain alignment of the substrate layers and/or engagement of the substrate with the curved surface.
  • the gap in the thickness direction of the substrate, may be in the range, for example, from about 1 micrometer to about 100 micrometers, from about 2 micrometers to about 50 micrometers, or from about 5 micrometers to about 25 micrometers. In some embodiments, the gap is no greater than about 100 micrometers, no greater than about 50 micrometers, no greater than about 30 micrometers, or no greater than about 25 micrometers.
  • FIG.3A is a schematic cross-sectional view of another embodiment of a diagnostic device 300 according to the present disclosure.
  • a curling mechanism is provided that includes a first curved layer 32a and a second curved layer 32b laminated with each other.
  • An elongated porous substrate such as the substrate 10 is positioned between the first and second curved layers 32a, 32b to form the diagnostic device 300.
  • the first curved layer 32a and the second curved layer 32b are curled along the longitudinal direction (e.g., the x axis) such that the substrate 10 is curved to deviate from its original straight longitudinal direction.
  • FIG.3B is a schematic cross-sectional view of another embodiment of a diagnostic device 300’ according to the present disclosure.
  • a curling mechanism includes a first curved layer 34a and a second curved layer 34b laminated with each other.
  • An elongated porous substrate such as the substrate 10 is positioned between the first and second curved layers 34a, 34b to form the diagnostic device 300’.
  • the first curved layer 34a and the second curved layer 32b are curled along a cross direction (e.g., the z axis) substantially normal to the longitudinal direction (e.g., the x axis) such that the substrate 10 is curved to deviate from its original straight cross direction.
  • the elongated porous substrate can be laminated between the first and second curved layers via an adhesive.
  • the first and second curved layers can be sufficiently rigid to maintain the substrate in its curved state.
  • the first and second curved layers each may be formed from a thermoplastic polymer such as, for example, PET.
  • one or more of the curved layers may also be formed from a cardboard, metal foil, etc.
  • FIG.4 is a schematic cross-sectional view of another embodiment of a diagnostic device 400 according to the present disclosure.
  • a curling mechanism is provided that includes a core 410 having an outer surface 412 which is a curved surface.
  • the core 410 can be made from a paper (cardboard) cylinder, which could be extended to a cardboard hemisphere.
  • the curved surface 412 may also be made from thin aluminum sheets.
  • a suitable thickness of the aluminum sheet may be from 0.010” to 0.025”.
  • An elongate porous substrate such as the substrate 10 at least partially wraps around the outer surface 412 of the core 410.
  • the core 410 may be any suitable shapes or geometries and can be made of any suitable materials as long as the outer surface 412 is sufficiently stiff to maintain the substrate 10 in the curved state.
  • a tape 414 is provided to laminate the elongated porous substrate 10 on the outer surface 412 of the core 410.
  • any suitable connection mechanism such as, for example, adhesive materials, mechanical fasteners, alone or in combination can be used to wrap the substrate 10 on the outer surface 412 of the core 410.
  • FIG.5 is a schematic cross-sectional view of another embodiment of a diagnostic device 500 according to the present disclosure.
  • the diagnostic device 500 includes an elongate, substantially planar porous substrate 50 extending along a longitudinal direction between a first end 511 and a second end 513 thereof.
  • the substrate 50 wraps around the curved surface 512 of a core 510 to form a roll having a plurality of revolutions where the adjacent revolutions of the roll 50 of substrate overlie with each other.
  • Any suitable connection mechanism can be used, including, for example, adhesive materials, mechanical fasteners, alone or in combination, to can be used to restrain the relative movements of the revolutions of the substrate 50.
  • adhesives can be applied at the first end 511 and/or the second end 513.
  • the substrate 50 When the substrate 50 is mounted on the outer surface of the core 510, a tension is applied such that the elongated porous substrate is in a curved state to create a tension to press the first portion and the second portion together.
  • the roll revolutions are held under compression to keep the adjacent layers in proximity and reduce the gap therebetween.
  • the substrate 50 includes multiple hydrophilic regions 522 which are distributed along a longitudinal direction of the substrate 50, and hydrophobic regions (e.g., portions of the substrate 50 not marked as the hydrophilic regions) adjacent to the hydrophilic regions 522.
  • the hydrophobic regions may be formed by applying a desired pattern of a low surface energy polymeric material such as, for example, a polymeric ink composition, to a hydrophilic substrate.
  • FIG.6 is a schematic cross-sectional view of another embodiment of a diagnostic device 600 according to the present disclosure.
  • the diagnostic device 600 includes an elongate, substantially planar porous substrate 60 extending along a longitudinal direction between a first end 611 and a second end 613 thereof.
  • the substrate 60 wraps around the curved surface 612 of a core 610 to form a roll having a plurality of revolutions where the adjacent revolutions of the roll 50 of substrate overlie with each other.
  • the substrate 60 includes multiple hydrophilic regions 622 which are distributed along a longitudinal direction of the substrate 60, and hydrophobic regions (e.g., portions of the substrate 60 not marked as the hydrophilic regions) adjacent to the hydrophilic regions 622.
  • the hydrophobic regions may be formed by applying a desired pattern of a low surface energy polymeric material such as, for example, a polymeric ink composition, to a hydrophilic substrate.
  • the hydrophilic regions 622 can be pre- registered before wrapping around the curved surface 612 such that various sample flow paths can be formed when the device 600 is assembled.
  • the various sample flow paths include one or more vertical sample flow path fluidly connecting aligned hydrophilic regions of adjacent revolutions, and one or more lateral sample flow paths each within a hydrophilic region extending in the tangential direction of the substrate roll 60.
  • the various sample flow paths can be combined in any desired manner to control flow for testing analytes.
  • the device 600 allows for routing a sample fluid flow from a sample port along a vertical sample flow path (e.g., the path as indicated by an arrow a1) to the inside of the device (e.g., a lateral sample flow path as indicated by an arrow a2) where it reacts with reagents and flows along a vertical sample flow path (e.g., the path as indicated by an arrow a3) back up to a color indicating or readout area (e.g., a lateral sample flow path as indicated by an arrow a4), then back to the inside of the device via a vertical sample flow path (e.g., the path as indicated by an arrow a5) and back up for indication of the volume of the liquid that flowed through the device (e.g., via a lateral sample flow path as indicated by an arrow a6, and a vertical sample flow path as indicated by an arrow a7).
  • a vertical sample flow path e.g., the path as indicated by an arrow a1
  • FIG. 1 is a diagnostic device comprising: an elongate porous substrate comprising a first portion in a first plane and a second portion in a second plane substantially parallel to the first plane, wherein the first portion overlies the second portion, the first portion comprises a first hydrophilic region, the second portion comprises a second hydrophilic region, the first and second hydrophilic regions are aligned to provide a sample flow path between the first portion of the substrate and the second portion of the substrate along a direction substantially normal to the first plane and the second plane; and a curling mechanism comprising a curved surface, wherein the elongate porous substrate is laminated on the curved surface, and the elongate porous substrate is in a curved state to create a tension to press the first portion and the second portion together.
  • Embodiment 2 is the diagnostic device of embodiment 1, wherein the substrate comprises at least one folded region, and the substrate is folded along the least one folded region to form the overlying first and second portions.
  • Embodiment 3 is the diagnostic device of embodiment 1 or 2, wherein the curling mechanism comprises a curved layer, the elongate porous substrate being positioned on an outer surface of the curved layer.
  • Embodiment 4 is the diagnostic device of embodiment 1 or 2, wherein the curling mechanism comprises a first curved layer and a second curved layer laminated with each other, the elongate porous substrate being positioned between the first and second curved layers.
  • Embodiment 5 is the diagnostic device of embodiment 4, wherein the elongated porous substrate is laminated between the first and second curved layers via an adhesive.
  • Embodiment 6 is the diagnostic device of embodiment 4 or 5, wherein the first curved layer and the second curved layer are curled along a longitudinal direction of the substrate.
  • Embodiment 7 is the diagnostic device of embodiment 4 or 5, wherein the first curved layer and the second curved layer are curled along a cross direction substantially normal to a longitudinal direction of the substrate.
  • Embodiment 8 is the diagnostic device of any one of embodiments 1-7, wherein the curling mechanism comprises a curved core having an outer surface which is the curved surface, and the elongate porous substrate at least partially wraps around the outer surface of the curved core.
  • Embodiment 9 is the diagnostic device of embodiment 8, wherein the elongate porous substrate wraps around the curved core to form a roll having a plurality of revolutions.
  • Embodiment 10 is the diagnostic device of embodiment 9, wherein the first hydrophilic region of the first portion of the substrate and the second hydrophilic region of the second portion of the substrate lie in the respective adjacent revolutions of the roll.
  • Embodiment 11 is the diagnostic device of any one of embodiments 1-10, further comprising one or more connective regions between the first portion of the substrate and the second portion of the substrate.
  • Embodiment 12 is the diagnostic device of any one of embodiments 1-11, further comprising a tape to laminate the elongate porous substrate on the outer surface of the curved core.
  • Embodiment 13 is the diagnostic device of any one of embodiments 1-12, wherein the first portion further comprises a first hydrophobic region adjacent to the second hydrophilic region of the second portion to provide a second sample flow path within the second hydrophilic region of the second portion along a direction substantially parallel to the second plane, the second sample flow path fluidly connected to the first sample flow path.
  • Embodiment 14 is a method of making a diagnostic device, the method comprising: providing an elongate, substantially planar porous substrate comprising a first portion in a first plane and a second portion in a second plane substantially parallel to the first plane, wherein the first portion overlies the second portion, the first portion comprises a first hydrophilic region, the second portion comprises a second hydrophilic region, the first and second hydrophilic regions are aligned to provide a first sample flow path between the first portion of the substrate and the second portion of the substrate along a direction substantially normal to the first plane and the second plane; and laminating the elongate porous substrate on a curved surface of a curling mechanism such that the elongate porous substrate is in a curved state to create a tension to press the first portion and the second portion together.
  • Embodiment 15 is the method of embodiment 14, wherein providing the substrate comprises folding the substrate along at least one folded region such that the first portion overlies the second portion.
  • Embodiment 16 is the method of embodiment 14 or 15, wherein laminating the substrate on the curved surface of the curling mechanism comprises positioning the substrate on an outer surface of a first curved layer, or between the first curved layer and a second curved layer laminated with each other.
  • Embodiment 17 is the method of embodiment 16, wherein the elongate porous substrate is positioned via an adhesive.
  • Embodiment 18 is the method of embodiment 16 or 17, wherein at least one of the first curved layer and the second curved layer is curled along a longitudinal direction of the substrate.
  • Embodiment 19 is the method of embodiment 16 or 17, wherein at least one of the first curved layer and the second curved layer is curled along a cross direction substantially normal to a longitudinal direction of the substrate.
  • Embodiment 20 is the method of any one of embodiment 14-19, wherein the curling mechanism comprises a curved core having an outer surface which is the curved surface, and the elongate porous substrate at least partially wraps around the outer surface of the curved core.
  • Embodiment 21 is the method of embodiment 20, wherein the elongate porous substrate wraps around the curved core to form a roll having a plurality of revolutions.
  • Embodiment 22 is the method of embodiment 21, wherein the first hydrophilic region of the first portion of the substrate and the second hydrophilic region of the second portion of the substrate lie in the respective adjacent revolutions of the roll.
  • Embodiment 23 is the method of any one of embodiment 14-22, further comprising providing one or more connective regions between the first portion of the substrate and the second portion of the substrate.
  • Embodiment 24 is the method of any one of embodiment 14-23, further comprising laminating a tape to cover the elongate porous substrate on curved surface.
  • Embodiment 25 is the method of any one of embodiment 14-24, wherein the first portion further comprises a first hydrophobic region adjacent to the second hydrophilic region of the second portion to provide a second sample flow path within the second hydrophilic region of the second portion along a direction substantially parallel to the second plane, the second sample flow path fluidly connected to the first sample flow path.
  • step (1) a hydrophobic ink available from Flint Group under the trade designation Easy Release (UVF03408) UV curable ink was flexographically printed using a 12 BCM/in 2 anilox roll and a patterned with a LUX ITP60 flexographic printing plate (MacDermid Graphics Solutions) at 20 ft/min onto Great Lakes Filter Paper (Grade: CP51232 – Grade 601) obtained from Ahlstrom- Munksjo Filtration LLC), and the ink was transported to the UV curing station and solidified. The time between printing and curing was such that when the paper was transported at 20 ft/min, it provided enough time for the ink to wick approximately half the thickness of the filter paper.
  • Easy Release UV curable ink was flexographically printed using a 12 BCM/in 2 anilox roll and a patterned with a LUX ITP60 flexographic printing plate (MacDermid Graphics Solutions) at 20 ft/min onto Great Lakes Filter Paper (Grade: CP51232
  • step (2) the printed paper from step (1) was then re-inserted through the printing line at 20 ft/min, and a second matching reverse-image pattern of the Flint Group Easy Release ink was printed in registration to the backside (i.e. opposing paper surface to the first pass of printing) of the filter paper.
  • the printing was performed with a 12 BCM/in 2 anilox roll and patterned LUX ITP60 flexographic printing plate.
  • the printed paper was transported to the UV curing station and solidified at 20 ft/min, which was sufficient time for the hydrophobic ink to penetrate the paper and reach the other half-printed hydrophobic barrier layer, completing a barrier layer for a diagnostic device.
  • the folded paper diagnostic device and blotting pad was then bent and attached to the surface of a 4 ounce glass bottle from FisherBrand with the ends of the box sealing tape attaching the curved paper device and blotting pad to curved surface of the glass bottle.
  • the glass bottle had a radius of curvature of approximately 1 inch, and a photo of the attached device is shown in FIG.8.
  • An opening was cut into the box sealing tape to access one of the two hydrophilic ports, and 50uL of blue-dyed water was applied to the hydrophilic port.
  • the liquid rapidly flowed through the port to the underlying blotting pad, and FIG.9 shows the unfolded paper device and blotting pad after separation it from the curved glass bottle.
  • step (1) a hydrophobic ink available from Flint Group under the trade designation Easy Release (UVF03408) UV curable ink was flexographically printed using a 12 BCM/in2 anilox roll and a patterned with a LUX ITP60 flexographic printing plate (MacDermid Graphics Solutions) at 20 ft/min onto Great Lakes Filter Paper (Grade: CP51232 – Grade 601) obtained from Ahlstrom- Munksjo Filtration LLC), and the ink was transported to the UV curing station and solidified. The time between printing and curing was such that when the paper was transported at 20 ft/min, it provided enough time for the ink to wick approximately half the thickness of the filter paper.
  • Easy Release UV curable ink was flexographically printed using a 12 BCM/in2 anilox roll and a patterned with a LUX ITP60 flexographic printing plate (MacDermid Graphics Solutions) at 20 ft/min onto Great Lakes Filter Paper (Grade: CP51232
  • step (2) the printed paper from step (1) was then re-inserted through the printing line at 20 ft/min, and a second matching reverse-image pattern of the Flint Group Easy Release ink was printed in registration to the backside (i.e. opposing paper surface to the first pass of printing) of the filter paper.
  • the printing was performed with a 12 BCM/in 2 anilox roll and patterned LUX ITP60 flexographic printing plate.
  • the printed paper was transported to the UV curing station and solidified at 20 ft/min, which was sufficient time for the hydrophobic ink to penetrate the paper and reach the other half-printed hydrophobic barrier layer, completing a barrier layer for a diagnostic device.
  • FIG.7 The pattern of hydrophobic ink that was printed on each side of the paper is shown in FIG.7, where each of the four panels are approximately 14.2 mm wide and 38.1 mm tall, leaving a hydrophilic port region with a diameter of approximately 4 to 4.5mm in diameter.
  • the hydrophobic regions and the hydrophilic regions are marked in FIG.7 as 74 and 72, respectively.
  • the paper device was then folded along the folding axes 76 to create a four-layer stack that was then attached to a 3mm thick cellulose blotting pad with a box sealing tape. The box sealing tape was placed over the folded device and was attached the flat surface of the blotting pad.
  • the paper device and blotting pad was left in a planar state, with no bending applied to the device and blotting pad, as shown in FIG 10.
  • An opening was cut into the box sealing tape to access one of the two hydrophilic ports, and 50uL of blue-dyed water was applied to the hydrophilic port.
  • the liquid appeared to stall and stop flowing through the device, and it appeared as if the layers of the folded device were separately slightly when the paper device was viewed at a low angle relative to the blotting pad.
  • the box sealing tape was then peeled away from the paper device and blotting pad, and the device was opened to visualize the flow path of blue-dyed water.
  • FIG.11 shows the paper device and blotting pad opened, and one can see where the liquid stopped flowing through the device.

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Abstract

L'invention concerne des dispositifs de diagnostic incurvés pour l'analyse quantitative ou qualitative d'un échantillon de fluide, ainsi que des procédés de fabrication et d'utilisation de ces dispositifs. Les dispositifs comprennent plusieurs couches ou portions empilées faites d'un matériau hydrophile. Les couches ou portions adjacentes comprennent chacune une région hydrophile qui est alignée pour fournir un trajet d'écoulement vertical de l'échantillon. Les couches empilées sont laminées sur une surface incurvée de telle sorte qu'elles se trouvent dans un état incurvé pour créer une tension permettant de presser les couches adjacentes ensemble.
PCT/IB2022/052855 2021-03-31 2022-03-28 Dispositif de diagnostic incurvé WO2022208321A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230120911A1 (en) 2020-03-31 2023-04-20 3M Innovative Properties Company Diagnostic Device

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Publication number Priority date Publication date Assignee Title
WO2001002093A2 (fr) * 1999-07-07 2001-01-11 3M Innovative Properties Company Article de detection comprenant une couche mince de commande d'ecoulement de fluide
US20130078711A1 (en) * 2011-09-23 2013-03-28 Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations Systems and methods for providing microfluidic devices
WO2013158827A1 (fr) * 2012-04-18 2013-10-24 Board Of Regents, The University Of Texas System Procédé pour détecter et quantifier des analytes en utilisant des dispositifs à base de papier tridimensionnels

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WO2001002093A2 (fr) * 1999-07-07 2001-01-11 3M Innovative Properties Company Article de detection comprenant une couche mince de commande d'ecoulement de fluide
US20130078711A1 (en) * 2011-09-23 2013-03-28 Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations Systems and methods for providing microfluidic devices
WO2013158827A1 (fr) * 2012-04-18 2013-10-24 Board Of Regents, The University Of Texas System Procédé pour détecter et quantifier des analytes en utilisant des dispositifs à base de papier tridimensionnels

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Title
WANG SHUQI ET AL: "Flexible Substrate-Based Devices for Point-of-Care Diagnostics", TRENDS IN BIOTECHNOLOGY, vol. 34, no. 11, 1 November 2016 (2016-11-01), pages 909 - 921, XP029778358, ISSN: 0167-7799, DOI: 10.1016/J.TIBTECH.2016.05.009 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230120911A1 (en) 2020-03-31 2023-04-20 3M Innovative Properties Company Diagnostic Device
US11744915B2 (en) 2020-03-31 2023-09-05 3M Innovative Properties Company Diagnostic device

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