WO2018153950A1 - Microfluidic test device - Google Patents

Microfluidic test device Download PDF

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Publication number
WO2018153950A1
WO2018153950A1 PCT/EP2018/054330 EP2018054330W WO2018153950A1 WO 2018153950 A1 WO2018153950 A1 WO 2018153950A1 EP 2018054330 W EP2018054330 W EP 2018054330W WO 2018153950 A1 WO2018153950 A1 WO 2018153950A1
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WO
WIPO (PCT)
Prior art keywords
primary
chamber
test device
fluid path
microfluidic
Prior art date
Application number
PCT/EP2018/054330
Other languages
French (fr)
Inventor
Indrek Tulp
Clemens KREMER
Tamás PARDY
Original Assignee
Selfdiagnostics Deutschland Gmbh
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 Selfdiagnostics Deutschland Gmbh filed Critical Selfdiagnostics Deutschland Gmbh
Publication of WO2018153950A1 publication Critical patent/WO2018153950A1/en

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Classifications

    • 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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • 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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • 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
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/18—Means for temperature control

Definitions

  • the present disclosure relates to a microfluidic test device, in particular a microfluidic test device for testing body fluids, such as urine and blood.
  • POCT point-of-care-testing
  • the traditional diagnosis of e.g. infections typically involves collection of a sample.
  • Most modern laboratories still use traditional testing methods such as cell culture and antigen based detection.
  • the cell culture method is highly specific, but has very low sensitivity, is expensive, slow (takes days) and requires special sample collection, storage, and transport.
  • Immunological assays like the enzyme immunoassay and direct fluorescent antibody (DFA) assay have low sensitivity and specificity as a cell culture method, which limits the use of these tests in diagnostic field.
  • DFA direct fluorescent antibody
  • NAATs nucleic acid amplification tests
  • a microfluidic test device comprising a body; a first chamber having an outlet optionally provided with a first valve and holding a first buffer having a first buffer volume; and a primary reaction chamber.
  • the microfluidic test device comprises a sample inlet for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device; a first fluid path connecting the outlet of the first chamber and the sample inlet; and a second fluid path connecting the sample inlet and the primary reaction chamber.
  • the microfluidic test device comprises a primary test part comprising a primary test chamber; a third primary fluid path connecting the primary reaction chamber and the primary test part; a primary valve arranged in the third primary fluid path; and a flow driving device configured to move fluid from the primary reaction chamber to the primary test part.
  • the microfluidic test device optionally comprises a heating assembly configured to heat a reaction fluid in the primary reaction chamber.
  • microfluidic test system comprising a microfluidic test device as disclosed herein and a sample plug.
  • Fig. 1 schematically illustrates an exemplary microfluidic test device
  • Fig. 2 is a schematic cross-sectional view of an exemplary microfluidic test device
  • Fig. 3 schematically illustrates an exemplary microfluidic test device
  • Fig. 4 is a perspective view of exemplary microfluidic test device
  • Fig. 5 is another perspective view of exemplary microfluidic test device
  • Fig. 6 is a perspective view of exemplary body of microfluidic test device
  • Fig. 7 is another perspective view of exemplary body of microfluidic test device
  • Fig. 8 is a second (bottom) view of exemplary body of microfluidic test device
  • Fig. 9 is a cut out view of exemplary microfluidic test device
  • Fig. 10 is a second (bottom) view of exemplary body of microfluidic test device, DETAILED DESCRIPTION
  • the microfluidic test device may be a point-of-care (POC) microfluidic test device.
  • Point-of-care testing (POCT), or bedside testing is defined as medical diagnostic testing at or near the point of care - that is, at the time and place of patient care. This contrasts with the historical pattern in which testing was wholly or mostly confined to the medical laboratory, which entailed sending off specimens away from the point of care and then waiting hours or days to learn the results, during which time care must continue without the desired information.
  • Point-of-care tests are simple medical tests that can be performed at the bedside.
  • the microfluidic test device may comprise a housing, wherein the body, e.g . with foils, is accommodated within the housing.
  • the housing may have one or more openings to allow access to the inside of the housing, e.g. to the sample inlet.
  • One or more button members may be included in the housing.
  • a first button of the housing may be associated with the first chamber and/or a second button of the housing may be associated with the flow driving device.
  • the microfluidic test device comprises a body.
  • the body may be an elongated body having a first end and a second end.
  • the body may have a first end surface and/or a second end surface.
  • the body may have one or more first surfaces, e.g. a first primary surface and/or a first secondary surface, and one or more second surface(s).
  • the first surface(s) may be intended for facing upwards when the microfluidic test device is positioned in a test position.
  • the second surface(s) may be intended for facing downwards when the microfluidic test device is positioned in a test position.
  • the body may comprise one or more grooves or recesses, also denoted first groove(s), in the first surface(s).
  • the body may comprise one or more grooves or recesses, also denoted second groove(s), in the second surface(s).
  • the first and/or second grooves may form at least a part of the fluid paths of the microfluidic test device.
  • the body may have one or more through-going bores from first surface(s) to second surface(s).
  • the body one or more through-going bores may form at least a part of the fluid paths of the microfluidic test device.
  • the body may be made of a body material.
  • the body material may be glass, silicon, or a polymer, such as Polydimethylsiloxane (PDMS).
  • PDMS Polydimethylsiloxane
  • the body is made of polypropylene (PP).
  • PP polypropylene
  • the body material may be black or grey. A black or grey PP body material is cheap and has good laser welding properties, in turn reducing welding time.
  • the microfluidic test device may comprise one or more first foils, such as a first primary foil and/or a first secondary foil, attached to the first surface(s) of the body.
  • the microfluidic test device may comprise one or more second foils, such as a second primary foil and/or a second secondary foil, on the second surface(s) of the body.
  • the first foil(s) and/or the second foil(s) may be attached to the body by laser welding.
  • the first foil(s) may have a thickness in the range from 0.05 mm to 2 mm, such as from 0.2 mm to 0.8 mm .
  • the second foil(s) may have a thickness in the range from 0.05 mm to 2 mm, such as from 0.2 mm to 1.0 mm .
  • a foil such as one or more first foils and/or one or more second foil(s) may be made of a flexible material.
  • the microfluidic test device may comprise a first primary foil attached to the first primary surface of the body.
  • the first primary foil may be made of a first primary foil material.
  • the first primary foil material may be the same as the body material, e.g. to facilitate attachment of the first primary foil to the body.
  • the first primary foil material may be a polymer, such as Polydimethylsiloxane (PDMS).
  • PDMS Polydimethylsiloxane
  • the first primary foil is made of polypropylene (PP).
  • PP polypropylene
  • the first primary foil material may be transparent. A transparent first primary foil material allows a user to inspect or follow liquid flow in fluid paths partly formed by the first primary foil. Further, a user can read test results through a transparent first primary foil material covering and/or sealing one or more openings in the body.
  • the microfluidic test device may comprise a first secondary foil attached to the first secondary surface of the body.
  • the first secondary foil may be made of a first secondary foil material.
  • the first secondary foil material may be metal material or an alloy.
  • the first secondary foil is made of aluminium.
  • the microfluidic test device may comprise a second primary foil attached to the second surface of the body.
  • the second primary foil may be made of a second primary foil material.
  • the second primary foil material may be the same as the body material, e.g. to facilitate attachment of the second primary foil to the body.
  • the second primary foil material may be a polymer, such as Polydimethylsiloxane (PDMS).
  • PDMS Polydimethylsiloxane
  • the second primary foil is made of polypropylene (PP).
  • the second primary foil material may be transparent. A transparent second primary foil material allows a user to inspect or follow liquid flow in fluid paths partly formed by the second primary foil.
  • the microfluidic test device comprises a first chamber having an outlet and holding a first buffer having a first buffer volume.
  • the outlet of the first chamber may be provided with a first valve.
  • the first valve may be configured to open when the pressure on the inlet side of the first valve is larger than a first pressure threshold.
  • the first chamber may have a first volume in the range from 10 microliters to 900 microliters.
  • the first chamber has a first volume in the range from 30 microliters to 1,000 microliters, such as 300 microliters, 400 microliters, 500 microliters, or 600 microliters, 700 microliters, 800 microliters, 900 microliters, or any ranges therebetween.
  • the first buffer may comprise components useful in amplifying a nucleotide target in the sample.
  • amplification is provided by Loop-mediated isothermal amplification (LAMP).
  • LAMP Loop-mediated isothermal amplification
  • the target sequence is amplified at a constant temperature typically 60-65 °C using either two or three sets of primers and a polymerase with high strand displacement activity in addition to a replication activity.
  • 4 different primers are used to identify 6 distinct regions on the target gene, which adds highly to the specificity.
  • An additional pair of "loop primers" can further accelerate the reaction. Due to the specific nature of the action of these primers, the amount of DNA produced in LAMP is considerably higher than PCR based amplification.
  • the first buffer optionally comprises a neutral chemical compound with a positively charged cationic functional group such as a quaternary ammonium or phosphonium cation (generally: onium ions) which bears no hydrogen atom and optionally with a negatively charged functional group such as a carboxylate group which may not be adjacent to the cationic site.
  • the neutral chemical compound may be Betaine.
  • the first buffer optionally comprises one or more inorganic salts, such as but not limited to MgS0 4 and/or (NH 4 ) 2 S0 4 .
  • the microfluidic test device comprises one or more reaction chambers including a primary reaction chamber.
  • the primary reaction chamber may have a volume larger than 20 microliters and/or less than 500 microliters.
  • the primary reaction chamber may have a volume in the range from 40 microliters to 200 microliters, such as 50 microliters, 75 microliters, 100 microliters, 125 microliters, 150 microliters, 175 microliters, or any ranges therebetween.
  • the microfluidic test device may comprise a primary reaction chamber plug forming a part of the primary reaction chamber.
  • a microfluidic test device with reaction chamber plugs facilitates positioning of reaction material in reaction chamber(s).
  • a pellet with reaction material such as a primary pellet with primary reaction material may be placed in a primary reaction chamber body part followed by a closing of the primary reaction chamber with a primary reaction chamber plug.
  • the microfluidic test device may comprise reaction material arranged or deposited at different positions in the microfluidic test device.
  • the microfluidic test device may comprise a primary reaction material.
  • the primary reaction material may be arranged in the primary reaction chamber.
  • the primary reaction material optionally comprises short strands of RNA and/or DNA (generally about 18-22 bases) that serve as a starting point for DNA synthesis.
  • the primary reaction material comprises nucleoside triphosphate (NTP).
  • NTP nucleoside triphosphate
  • the primary reaction material comprises an enzyme capable of synthesising chains or polymers of nucleic acids, optionally in combination with NTP and/or short strands of RNA and/or DNA.
  • the enzyme capable of synthesising chains or polymers of nucleic acids may be a LAMP polymerase.
  • the primary reaction material may be subjected to a freeze-drying process to protect the reagents and ensure the stability and re-suspendability properties of the reagent(s) prior to the introduction of the reagent into the primary reaction chamber.
  • the primary reaction material is in a dry and/or pellet like form .
  • the primary reaction material may be coated onto a surface of the body and/or a foil of the microfluidic test device.
  • the microfluidic test device comprises a sample inlet for receiving a sample.
  • the sample inlet is configured for feeding a sample having a sample volume, into the medical test device.
  • the microfluidic test device comprises a first fluid path.
  • the first fluid path may connect the outlet of the first chamber and the sample inlet.
  • the first fluid path may comprise a first branch and a second branch in parallel to the first branch.
  • the first branch of the first fluid path may be connected to a first inlet of sample chamber formed by sample inlet and sample plug.
  • the first branch may feed first buffer into the sample chamber via first inlet.
  • the second branch of the second fluid path may be connected to a second inlet of sample chamber formed by sample inlet and sample plug.
  • the second branch of the first fluid path may feed first buffer into the sample chamber via second inlet.
  • a plurality of branches in the first fluid path, the branches connected to respective sample chamber inlets in the microfluidic test device provides improved flushing of the sample.
  • the sample chamber only has a single inlet.
  • the microfluidic test device comprises a second fluid path.
  • the second fluid path may connect the sample inlet and the primary reaction chamber.
  • the second fluid path may comprise a first branch and a second branch in parallel to the first branch.
  • the first branch and the second branch of the second fluid path are optionally connected to respective first outlet and second outlet of the sample chamber.
  • liquid from the sample chamber may enter the first branch and the second branch of the second fluid path via respective first outlet and second outlet of the sample chamber.
  • the first branch and the second branch of the second fluid path may be joined in second fluid path joint to a single fluid path part, optionally before splitting into second primary fluid path and second secondary fluid path.
  • the second primary fluid path is directly connected to first outlet of sample chamber and the second secondary fluid path is directly connected to the second outlet of sample chamber.
  • the sample chamber only has a single outlet that may later be branched into second primary fluid path and second secondary fluid path.
  • the microfluidic test device comprises a primary test part comprising a primary test chamber.
  • the microfluidic test device comprises a third primary fluid path optionally connecting the primary reaction chamber and the primary test part.
  • the microfluidic test device may comprise a primary valve arranged in the third primary fluid path.
  • the primary valve acts as a blocking mechanism to separate the primary test part and liquid (sample, first buffer and reaction material) during a reaction time.
  • the primary valve may be configured to open when the pressure on the inlet side of the primary valve is larger than a primary pressure threshold.
  • the microfluidic test device comprises a flow driving device configured to move fluid (primary test liquid) from the primary reaction chamber to the primary test part.
  • a user operating the flow driving device may be able to break or force primary valve to open.
  • the microfluidic test device optionally comprises a heating assembly configured to heat a (primary) reaction fluid in the primary reaction chamber.
  • the heating assembly may be configured to heat the (primary) reaction fluid in the primary reaction chamber to a primary reaction temperature in the range from 30°C to 100°C, preferably in the range from 30°C to 70°C, such as in the range from 45°C to 68°C.
  • the primary reaction temperature is in the range from 55°C to 65°C, such as from 58°C to 63°C.
  • the primary reaction temperature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C.
  • the heating assembly may comprise one or more heating elements, such as one or more primary heating elements, e.g. for heating the primary reaction chamber.
  • the heating assembly may comprise a primary heating element adjacent the primary reaction chamber.
  • the primary heating element may be configured to self-regulate to a primary temperature, e.g. upon application of a primary voltage.
  • the primary temperature may be in the range from 30°C to 100°C, preferably in the range from 30°C to 80°C, such as in the range from 45°C to 75°C.
  • the primary temperature is in the range from 55°C to 70°C, such as from 58°C to 67°C.
  • the primary temperature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C.
  • the primary voltage is in the range from 0.5V to 5V, such as in the range from 1.5V to 3.5 V, e.g. 3V
  • a self- regulating primary heating element reduces or eliminates the need for electrical control circuitry, in turn providing a simple temperature control.
  • the microflu idic test device may comprise a first terminal and a second terminal .
  • the primary heating element may be connected to the first term inal (first side and/or first end of primary heating element) and the second terminal (second side and/or second) end of primary heating element) for applying a voltage to the heating assembly, such as the primary heating element.
  • the heating assembly e.g . when configured for two-reaction cham ber heating, may have a length in the range from 15 mm to 50 mm, such as from 20 m m to 30 mm m e.g . 24 mm .
  • the heating assem bly e.g . when configured for two-reaction cham ber heating, may have a width in the range from 5 m m to 30 m m, such as from 10 mm to 20 mm m e.g . 11 m m .
  • the heating assembly may have a thickness in the range from 0.2 mm to 3 m m .
  • the heating assembly may comprise a first electrode layer arranged on a first side of the primary heating element.
  • the heating assem bly may com prise a second electrode layer arranged on a second side of the primary heating element.
  • the primary heating element may be sandwiched between the first electrode layer and second electrode layer for applying a primary voltage to the primary heating element.
  • the first electrode layer (and thus the primary heating element) and second electrode layer (and thus the primary heating element) may be respectively connected to first term ina l and second term ina l.
  • the first terminal and the second term inal may be arranged in a battery docket of the microflu idic test device.
  • the first term inal and the second terminal may be arranged in a connector for connecting an external power sou rce to the m icrofluidic test device.
  • the first electrode layer and/or the second electrode layer may be made of a su itable electrode material, such as copper, nickel or an alloy com prising copper and/or nickel .
  • the heating assembly e.g . first electrode layer of the heating assembly, may be attached to the second primary foil, e.g . by glu ing .
  • the heating assem bly may be adjacent to and/or overlapping the primary and secondary reaction chambers.
  • the primary heating element may com prise a resin material and/or one or more polymers.
  • the primary heating element may com prise a carbon-based heater resin .
  • the primary heating element may be made of a material with positive tem perature coefficient of resistance.
  • the primary heating element may com prise a ceramic element, such as a positive temperatu re coefficient (PCT) ceram ic.
  • the ceramic element may be made of, based on, or com prise bariu m titanate (BaTiOS).
  • the microfluidic test device com prises a secondary reaction chamber.
  • the secondary reaction chamber may have a volume larger than 20 microliters and/or less than 500 microliters.
  • the secondary reaction chamber may have a volume in the range from 40 microliters to 200 microliters, such as 50 microliters, 75 microliters, 100 microliters, 125 microliters, 150 microliters, 175 microliters, or any ranges therebetween.
  • the microfluidic test device may comprise a secondary reaction chamber plug forming a part of the secondary reaction chamber.
  • the second fluid path may connect the sample inlet and the secondary reaction chamber.
  • the second fluid path may be Y-shaped with a first end connected to the sample inlet, a primary second end connected to the primary test part, and a secondary second end connected to the secondary reaction chamber.
  • the microfluidic test device may comprise a secondary test part comprising a secondary test chamber.
  • the microfluidic test device may comprise a third secondary fluid path connecting the secondary test part and one or more reaction chambers, such as the primary reaction chamber and/or the secondary reaction chamber.
  • the microfluidic test device may comprise a secondary valve arranged in the third secondary fluid path.
  • the flow driving device may be configured to move fluid from the primary reaction chamber to the secondary test part.
  • the flow driving device may be configured to move fluid from the secondary reaction chamber to the secondary test part.
  • the secondary valve acts as a blocking mechanism to separate the secondary test part and liquid (sample, first buffer and reaction material) during a reaction time.
  • the secondary valve may be configured to open when the pressure on the inlet side of the secondary valve is larger than a secondary pressure threshold. Thus, a user operating the flow driving device may be able to break or force secondary valve to open.
  • the microfluidic test device may comprise a secondary reaction material.
  • the secondary reaction material may be arranged in the secondary reaction chamber.
  • the secondary reaction material may be the same as or different from the first reaction material.
  • the secondary reaction material optionally comprises short strands of RNA and/or DNA (generally about 18-22 bases) that serve as a starting point for DNA synthesis.
  • the secondary reaction material comprises nucleoside triphosphate (NTP).
  • NTP nucleoside triphosphate
  • the secondary reaction material comprises an enzyme capable of synthesising chains or polymers of nucleic acids, optionally in com bination with NTP and/or short strands of RNA and/or DNA.
  • the enzyme capable of synthesising chains or polymers of nucleic acids may be a LAMP polymerase.
  • the seconda ry reaction material may be su bjected to a freeze-drying process to protect the reagents and ensure the stability and re-suspendability properties of the reagent(s) prior to the introduction of the reagent into the secondary reaction cham ber.
  • the secondary reaction material is in a dry and/or pellet like form .
  • the heating assembly may be configured to heat a (secondary) reaction flu id in the secondary reaction chamber to a secondary reaction tem perature in the range from 30°C to 100°C, preferably in the range from 30°C to 70°C, such as in the range from 45°C to 68°C.
  • the secondary reaction temperature is in the range from 55°C to 65°C, such as from 58°C to 63°C.
  • the secondary reaction is in the range from 55°C to 65°C, such as from 58°C to 63°C.
  • tem perature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C.
  • the first primary heating element may be configured to heat the secondary reaction cham ber.
  • the heating assembly may com prise one or more heating elements, such as one or more secondary heating elements, e.g . for heating the secondary reaction cham ber.
  • the heating assem bly may com prise a seconda ry heating element adjacent the secondary reaction chamber.
  • the primary heating element may be adjacent the secondary reaction chamber.
  • the seconda ry heating element may com prise a resin material and/or one or more polymers.
  • the secondary heating element may com prise a carbon-based heater resin.
  • the secondary heating element may be made of a material with positive temperatu re coefficient of resistance.
  • the secondary heating element may comprise a ceram ic element, such as a positive temperatu re coefficient (PCT) ceram ic.
  • the ceramic element may be made of, based on, or com prise bariu m titanate (BaTiOS).
  • the secondary heating element may be configured to self-regu late to a secondary tem perature, e.g . u pon application of a secondary voltage.
  • the tem perature may be the same as or different from the primary temperatu re.
  • the secondary tem perature may be in the range from 30°C to 100°C, preferably in the range from 30°C to 80°C, such as in the range from 45°C to 75°C.
  • the primary temperatu re is in the range from 55°C to 70°C, such as from 58°C to 67°C.
  • the primary temperature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C.
  • the secondary voltage is the same as or different from the primary voltage.
  • the secondary voltage may be in the range from 0.5V to 5V, such as in the range from 1.5V to 3.5 V, such as 3V.
  • a self-regulating primary heating element reduces or eliminates the need for electrical control circuitry, in turn providing a simple temperature control.
  • the microfluidic test device enables different tests with different test temperatures in the same microfluidic test device.
  • Primary and/ secondary voltages less than 5V may be advantageous for a POCT device, e.g. for a battery-driven POCT device.
  • the flow driving device may comprise a second chamber having an outlet optionally provided with a second valve, wherein the outlet of the second chamber is connected to the first fluid path or the second fluid path.
  • the second valve may be configured to open when the pressure on the inlet side of the second valve is larger than a second pressure threshold.
  • the microfluidic test device may comprise a fourth fluid path connecting the outlet of the second chamber and the first fluid path or the second fluid path.
  • the second chamber has a second volume in the range from 30 microliters to 2,000 microliters, such as 300 microliters, 400 microliters, 500 microliters, 600 microliters, 800 microliters, 1,000 microliters, 1,20 microliters, 1,400 microliters, 1,600 microliters, 1,800 microliters, or any ranges therebetween.
  • the microfluidic test device may comprise a second fluid, such as air and/or liquid in the second chamber.
  • the microfluidic test system may comprise a seal covering the sample inlet.
  • the seal may be peeled off, removed or broken prior to or just prior to testing by inserting a sample plug into the microfluidic test device.
  • the risk of contaminating the inside of the microfluidic test device may be reduced.
  • a test part of the microfluidic test device such as the primary test part and/or the secondary test part may comprise a second lateral flow strip.
  • the primary test part may comprise a first lateral flow strip having a first end connected to or inserted into an outlet of the primary test chamber.
  • the secondary test part may comprise a second lateral flow strip having a first end connected to or inserted into an outlet of the secondary test chamber.
  • a plurality of lateral flow strips enables detection of faulty tests and/or enables performance of different tests on a single sample.
  • the first lateral flow strip may have a length in the range from 30 mm to 100 mm, such as in the range from 40 to 80 mm. In one or more exemplary microfluidic test devices, the first lateral flow strip has a length in the range from 60 mm to 70 mm .
  • the first lateral flow strip may have a width in the range from 1 mm to 10 mm, such as in the range from 1.5 mm to 4.0 mm. Narrow lateral flow strips have reduced requirements for liquid volume. In one or more exemplary microfluidic test devices, the first lateral flow strip has a width in the range from 2.0 mm to 3.5 mm, such as 3.0 mm .
  • the second lateral flow strip may have a length in the range from 30 mm to 100 mm, such as in the range from 40 to 80 mm. In one or more exemplary microfluidic test devices, the second lateral flow strip has a length in the range from 60 mm to 70 mm.
  • the second lateral flow strip may have a width in the range from 1 mm to 10 mm, such as in the range from 1.5 mm to 4.0 mm. Narrow lateral flow strips have reduced requirements for liquid volume. In one or more exemplary microfluidic test devices, the second lateral flow strip has a width in the range from 2.0 mm to 3.5 mm, such as 3.0 mm .
  • Lateral flow strips in the present context are simple devices intended to detect the presence (or absence) of a target analyte in sample (matrix) without the need for specialized and costly equipment.
  • these tests are used for medical diagnostics either for home testing, point of care testing, or laboratory use.
  • a widely spread and well known application is the home pregnancy test.
  • the technology is based on a series of capillary beds, such as pieces of porous paper or sintered polymer.
  • Each of these elements has the capacity to transport fluid (e.g., urine) spontaneously.
  • the first element acts as a sponge and holds an excess of sample fluid. Once soaked, the fluid migrates to the second element (conjugate pad) in which the manufacturer has stored the so-called conjugate, a dried format of bio-active particles in a salt-sugar matrix that contains everything to guarantee an optimized chemical reaction between the target molecule and its chemical partner that has been immobilized on the particle's surface.
  • the sample fluid dissolves the salt-sugar matrix, it also dissolves the particles and in one combined transport action the sample and conjugate mix while flowing through the porous structure.
  • the analyte binds to the particles while migrating further through the third capillary bed.
  • This material has one or more areas (often called stripes) where a third molecule has been immobilized by the manufacturer.
  • stripes areas where a third molecule has been immobilized by the manufacturer.
  • haptens can be used for the labelling of the primers, including FAM, biotin, DIG, to detect amplification product with lateral flow strips. Using different hapten combination multiple product detection can be achieved (multiplex reaction detecting several different pathogens at once).
  • the body may comprise a first valve body part forming a part of the first valve.
  • the first valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the body may comprise a second valve body part forming a part of the second valve.
  • the second valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the body may comprise a primary valve body part forming a part of the primary valve.
  • the primary valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the body may comprise a secondary valve body part forming a part of the secondary valve.
  • the secondary valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the body may comprise a primary test chamber body part forming a part of the primary test chamber.
  • the primary test chamber body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the body may comprise a secondary test chamber body part forming a part of the secondary test chamber.
  • the secondary test chamber body part may be formed as a recess in a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the body/microfluidic test device may comprise a first flow strip chamber and/or a second flow strip chamber.
  • the first flow strip chamber may be accessible, e.g. for reading test results, through a first opening in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the second flow strip chamber may be accessible, e.g. for reading test results, through a second opening 70 in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
  • the body may comprise one or more holding elements for holding and/or fixate lateral flow strip(s) in position, e.g. between the body and a second foil, such as a second primary foil.
  • the body may comprise one or more first holding elements, such as a first primary holding element and/or a first secondary holding element, in the first flow strip chamber, optionally configured to hold or fixate a first lateral flow strip in position between the body and the second primary foil.
  • the body may comprise one or more second holding elements, such as a second primary holding element and/or a second secondary holding element, in the second flow strip chamber, optionally configured to hold or fixate a second lateral flow strip in position between the body and the second primary foil.
  • the first primary foil may comprise a primary valve foil part forming a part of the primary valve.
  • the first primary foil may comprise a secondary valve foil part forming a part of the secondary valve.
  • the first primary foil may comprise a first primary test chamber foil part forming a part (top) of the primary test chamber.
  • the first primary foil may comprise a first secondary test chamber foil part forming a part (top) of the secondary test chamber.
  • the first primary foil may cover and/or seal the first opening in the body.
  • the first primary foil may cover and/or seal the second opening in the body.
  • the first secondary foil may comprise a first chamber foil part forming a part of the first chamber.
  • the first secondary foil may comprise a second chamber foil part forming a part of the second chamber.
  • the first secondary foil may comprise a first valve foil part forming a part of the first valve.
  • the first secondary foil may comprise a second valve foil part forming a part of the second valve.
  • the first primary foil and the first secondary foil may be made of different materials, e.g. to implement different functions in the microfluidic test device.
  • the second primary foil may comprise a second primary test chamber foil part forming a part (bottom) of the primary test chamber.
  • the second primary foil may comprise a second secondary test chamber foil part forming a part (bottom) of the secondary test chamber.
  • the second primary foil may comprise a primary reaction chamber foil part forming a part (bottom) of the primary reaction chamber.
  • the second primary foil may comprise a secondary reaction chamber foil part forming a part (bottom) of the secondary reaction chamber.
  • the heating assembly may be attached to the second primary foil. The heating assembly may partly or fully cover the primary reaction chamber foil part and/or the secondary reaction chamber foil part. Thus, efficient heat transfer to the reaction chambers are provided for.
  • the second primary foil may comprise a sample inlet foil part forming a part (bottom) of the sample inlet.
  • the second primary foil may comprise a first flow strip chamber foil part forming a part of the first flow strip chamber and/or a second flow strip chamber foil part forming a part of the second flow strip chamber.
  • the second primary foil may form a part of one or more fluid paths, such as the first, second, third (primary and secondary), and/or fourth fluid paths.
  • FIG. 1 schematically illustrates a first (top) view of an exemplary microfluidic test device.
  • the microfluidic test device 2 comprises a body 4 and a first chamber 6 having an outlet 8 provided with a first valve 10 and holding a first buffer having a first buffer volume.
  • the microfluidic test device 2 comprises a primary reaction chamber 12 and a sample inlet 14 for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device 2.
  • a first fluid path 16 connects the outlet 8 of the first chamber 6 and the sample inlet 14 and a second fluid path 18 connects the sample inlet 14 and the primary reaction chamber 12.
  • the microfluidic test device 2 comprises a primary test part 20 comprising a primary test chamber 22 with a third primary fluid path 24 connecting the primary reaction chamber 12 and the primary test part 20.
  • a primary valve 26 is arranged in the third primary fluid path 24.
  • the microfluidic test device 2 comprises a flow driving device 28 configured to move fluid from the primary reaction chamber 12 to the primary test part 20.
  • the flow driving device 28 comprises a second chamber 28A having an outlet optionally provided with a second valve 28B. The outlet of the second chamber is connected to the first fluid path 16 via fourth fluid path 29.
  • the microfluidic test device 2 comprises a heating assembly 30 configured to heat a reaction liquid in the primary reaction chamber 12.
  • the heating assembly 30 is connected to a power source (not shown).
  • the power source may be one or more batteries accommodated or inserted in the microfluidic test device.
  • the power source may be an external power source connected to the microfluidic test device via a connector (not shown).
  • the primary test part 20 comprises a first lateral flow strip 32 having a first end 34 connected to an outlet of the primary test chamber 22.
  • the first lateral flow strip 32 has a length of 65 mm and a width of 3.0 mm.
  • Fig. 2 shows an exemplary cross-sectional view of the microfluidic test device 2.
  • the body 4 has a first end 36 with a first end surface, and a second end 38 with a second end surface.
  • the body 4 has a first surface 40 intended for facing upwards when the microfluidic test device is positioned in a test position, and a second surface 42 opposite the first surface 40 and intended for facing downwards when the microfluidic test device is positioned in a test position.
  • the microfluidic test device comprises a first primary foil 44 attached to the first surface 40 of the body 4.
  • the first primary foil 44 forms a part of the third primary fluid path 24 and the primary valve 26.
  • the microfluidic test device comprises a first secondary foil 46 attached to the first surface 40 of the body 4.
  • the first secondary foil 46 forms a part of the first chamber 6 and the first valve 10.
  • the microfluidic test device comprises a first tertiary foil 47 attached to the first surface 40 of the body 4.
  • the first tertiary foil 47 forms a part of the flow driving device 28.
  • the flow driving device 28 is embodied as a second chamber with an outlet and a second valve arranged at the outlet of the second chamber.
  • the microfluidic test device comprises a second primary foil 48 attached to the second surface 42 of the body 4.
  • the first fluid path 16 connects the first chamber 6 and the bottom of sample inlet 14.
  • the second fluid path 18 connects the sample inlet 14 and the first reaction chamber 12.
  • first buffer can be moved from the first chamber 6 through the first fluid path 16 into the sample inlet 14 by pressing on the first secondary foil 46 with a force sufficient to open the first valve 10, i.e. a force to apply a first pressure larger than the first pressure threshold.
  • the first buffer thus flushes sample in the sample inlet 14 through the second fluid path 18 and into the first reaction chamber 12, where the first buffer, the sample and a primary reaction material are mixed.
  • the flow driving device 28 is activated by pressing on the first tertiary foil 47 with a force sufficient to open the second valve 28B, i.e. a force to apply a second pressure larger than the second pressure threshold.
  • a force sufficient to open the second valve 28B i.e. a force to apply a second pressure larger than the second pressure threshold.
  • Fig. 3 schematically illustrates a first (top) view of an exemplary microfluidic test device.
  • the microfluidic test device 2A comprises a body 4 and a first chamber 6 having an outlet 8 provided with a first valve 10 and holding a first buffer having a first buffer volume.
  • the microfluidic test device 2 comprises a primary reaction chamber 12 and a sample inlet 14 for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device 2.
  • a first fluid path 16 connects the outlet 8 of the first chamber 6 and the sample inlet 14 and a second fluid path 18 connects the sample inlet 14 and the primary reaction chamber 12.
  • the microfluidic test device 2 comprises a primary test part 20 comprising a primary test chamber 22 with a third primary fluid path 24 connecting the primary reaction chamber 12 and the primary test part 20.
  • a primary valve 26 is arranged in the third primary fluid path 24.
  • the microfluidic test device 2 comprises a flow driving device 28 configured to move fluid from the primary reaction chamber 12 to the primary test part 20, and a heating assembly 30 configured to heat a reaction fluid in the primary reaction chamber 12.
  • the primary test part 20 comprises a first lateral flow strip 32 having a first end 34 connected to an outlet of the primary test chamber 22.
  • the microfluidic test device 2A comprises a secondary reaction chamber 50, wherein the second fluid path 18 connects the sample inlet 14 and the secondary reaction chamber 50.
  • the microfluidic test device 2A comprises a secondary test part 52 comprising a secondary test chamber 54 with a third secondary fluid path 56 connecting the secondary reaction chamber 50 and the secondary test part 52.
  • a secondary valve 58 is arranged in the third secondary fluid path 56.
  • the flow driving device 28 is configured to move fluid from the secondary reaction chamber 50 to the secondary test part 52, and the heating assembly 30 is optionally configured to heat a reaction fluid in the secondary reaction chamber 50.
  • the secondary test part 52 comprises a second lateral flow strip 60 having a first end 62 connected to an outlet of the secondary test chamber 54.
  • the second lateral flow strip 60 has a length of 65 mm and a width of 3.0 mm .
  • Figs. 4-10 show different views of exemplary microfluidic test system(s) and parts thereof.
  • the microfluidic test system comprises a microfluidic test device (housing not shown) and a sample plug.
  • Figs. 4 and 5 show perspective views of parts of microfluidic test device 2B with a sample plug 63 inserted in the sample inlet of the microfluidic test device.
  • the microfluidic test device 2B comprises a body 4A and one or more foils attached to surfaces of the body.
  • the microfluidic test device 2B comprises a first primary foil 44 attached to a first primary surface 40A of the body 4A and forming a part of the third fluid paths (primary and secondary), the primary valve, and the secondary valve of the microfluidic test device 2B.
  • the first primary foil 44 optionally is a flexible plastic foil made of polypropylene that has been laser-welded to the body 4A made of polypropylene.
  • the microfluidic test device 2B comprises a first secondary foil 46 attached to a first secondary surface 40B (See Fig. 6) of the body 4A and forming a part of the first chamber 6, first valve 10, second chamber 28A, and second valve 28B.
  • the first secondary foil 46 optionally is a metal foil, such as an aluminium foil, and/or comprises one or more metal layers.
  • the first surfaces 40A, 40B are intended for facing upwards when the microfluidic test device 2B is positioned in a test position, and the second surface 42 is intended for facing downwards when the microfluidic test device 2B is positioned in a test position.
  • the microfluidic test device 2B comprises a second primary foil 48 attached to the second surface 42 (See Fig. 7) of the body 4A. Further, the microfluidic test device 2B comprises a heating assembly 30 comprising a primary heating element. The heating element is arranged on the second primary foil 48 adjacent the primary reaction chamber and the secondary reaction chamber and configured to heat the primary reaction chamber (and primary reaction liquid) and the secondary reaction chamber (and secondary reaction liquid).
  • the second primary foil 48 forms a part of the first, second, third (primary and secondary), and fourth fluid paths, primary reaction chamber, secondary reaction chamber, primary test chamber, secondary test chamber, and sample inlet (sample chamber).
  • the microfluidic test device 2B comprises a primary reaction chamber 12 and a sample inlet 14 for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device 2B.
  • the microfluidic test device 2B comprises a primary reaction chamber plug 12A forming a part of the primary reaction chamber 12.
  • the sample inlet 14 is configured for receiving the sample plug 63, the sample plug 63 carrying the sample.
  • a first fluid path connects the outlet of the first chamber 6 and the sample inlet 14 and a second fluid path connects the sample inlet 14 and the primary reaction chamber 12.
  • the microfluidic test device 2B comprises a primary test part comprising a primary test chamber and a first lateral flow strip with a third primary fluid path connecting the primary reaction chamber 12 and the primary test part (primary test chamber).
  • a primary valve is arranged in the third primary fluid path.
  • the microfluidic test device 2B comprises a flow driving device 28 configured to move fluid from the primary reaction chamber 12 to the primary test part.
  • the flow driving device 28 comprises a second chamber 28A having an outlet optionally provided with a second valve. The outlet of the second chamber is connected to the first fluid path via fourth fluid path.
  • the microfluidic test device 2B comprises a secondary reaction chamber 50, wherein the second fluid path connects the sample inlet 14 and the secondary reaction chamber 50.
  • the microfluidic test device 2B comprises a secondary reaction chamber plug 50A forming a part of the secondary reaction chamber 50.
  • the microfluidic test device 2B comprises a secondary test part comprising a secondary test chamber and a second lateral flow strip, with a third secondary fluid path connecting the secondary reaction chamber 50 and the secondary test part
  • a secondary valve is arranged in the third secondary fluid path.
  • the flow driving device 28 is configured to move fluid from the secondary reaction chamber 50 to the secondary test part.
  • Fig. 6 shows a perspective view of a body of the microfluidic test device.
  • a first valve body part 10A of the body 4A forms a part of the first valve 10.
  • the first valve body part 10A is formed as a recess in the first secondary surface 40B of the body 4A.
  • a first through-going bore 16A from the first secondary surface 40B to the second surface 42 forms a part of the first fluid path 18.
  • a primary reaction chamber body part 12B forms a part of the primary reaction chamber 12.
  • the primary reaction chamber body part 12B is formed as a through- going bore in the body with the primary reaction chamber plug 12A and the second primary foil 48 forming top and bottom of the primary reaction chamber 12.
  • a primary test chamber body part 22A of the body 4A forms a part of the primary test chamber 22.
  • the primary test chamber body part 22A is formed as a through-going bore from the first primary surface 40A to the second surface 42.
  • the first primary foil 44 and the second primary foil 48 form top and bottom of the primary test chamber 22.
  • a primary valve body part 26A of the body 4A forms a part of the primary valve 26.
  • the primary valve body part 26A is formed as a recess in the first primary surface 40A of the body 4A.
  • a primary through-going bore 24A from the first primary surface 40A to the second surface 42 forms a part of the third primary fluid path 24.
  • a second valve body part 28C of the body 4A forms a part of the second valve 28B.
  • the second valve body part 28C is formed as a recess in the first secondary surface 40B of the body 4A.
  • a fourth through-going bore 29A from the first secondary surface 40B to the second surface 42 forms a part of the fourth fluid path 29.
  • a secondary reaction chamber body part 50B forms a part of the secondary reaction chamber 50.
  • the secondary reaction chamber body part 50B is formed as a through- going bore in the body with the secondary reaction chamber plug 50A and the second primary foil 48 forming top and bottom of the secondary reaction chamber 50.
  • a secondary test chamber body part 54A of the body 4A forms a part of the secondary test chamber 54.
  • the secondary test chamber body part 54A is formed as a through- going bore from the first primary surface 40A to the second surface 42.
  • the first primary foil 44 and the second primary foil 48 form top and bottom of the secondary test chamber 54.
  • a secondary valve body part 58A of the body 4A forms a part of the secondary valve 58.
  • the secondary valve body part 58A is formed as a recess in the first primary surface 40A of the body 4A.
  • a secondary through-going bore 56A from the first primary surface 40A to the second surface 42 forms a part of the third secondary fluid path 56.
  • the microfluidic test device comprises a first flow strip chamber and a second flow strip chamber partly formed in the body 4A.
  • the first flow strip chamber is accessible through a first opening 68 in the first primary surface 40A
  • the second flow strip chamber is accessible through a second opening 70 in the first primary surface 40A.
  • the first and second openings enables optical readout of lateral flow strips.
  • Fig. 7 shows another perspective view of the body 4A, where a first recess 16B forms a part of the first fluid path 16 between the first chamber 6 and the sample inlet 14 partly formed by sample inlet body part 14A.
  • the second fluid path comprises a second primary fluid path 18A and a second secondary fluid path 18B.
  • the second primary fluid path 18A connects the sample inlet 14 and the primary reaction chamber 12, and the second secondary fluid path 18B connects the sample inlet 14 and the secondary reaction chamber 50.
  • a second primary recess 18C in the second surface 42 forms, together with the second primary foil 48, a part of the second primary fluid path 18A.
  • a second secondary recess 18D in the second surface 42 forms, together with the second primary foil 48, a part of the second secondary fluid path 18B.
  • a fourth recess 29B in the second surface 42 forms, together with the second primary foil 48, a part of the fourth fluid path 29.
  • the fourth fluid path 29 connects the outlet of the second chamber 28A at second valve 28B and the first fluid path 16.
  • a third primary recess 24B in the second surface 42 forms, together with the second primary foil 48, a part of the third primary fluid path 24.
  • a third secondary recess 56B in the second surface 42 forms, together with the second primary foil 48, a part of the third secondary fluid path 56.
  • a first strip chamber recess 64A forms a part of first flow strip chamber for
  • a second strip chamber recess 66A forms a part of second flow strip chamber 66 for accommodating a second lateral flow strip.
  • the second primary foil 48 forms the bottom of the flow strip chambers 64, 66.
  • a first end of the first lateral flow strip is arranged to overlap with the primary test chamber body part 22A such that test liquid in the primary test chamber 22 is fed to the first lateral flow strip.
  • a first end of the second lateral flow strip is arranged to overlap with the secondary test chamber body part 54A such that test liquid in the secondary test chamber 54 is fed to the second lateral flow strip.
  • First holding elements 72, 74 are provided in the first flow strip chamber 64 of the body 4A.
  • the first primary holding element 72 and the first secondary holding element 74 are configured to hold or fixate the first lateral flow strip in position between the body 4A and the second primary foil 48.
  • Second holding elements 76, 78 are provided in the second flow strip chamber 66 of the body 4A.
  • the second primary holding element 76 and the second secondary holding element 78 are configured to hold or fixate the second lateral flow strip in position between the body 4A and the second primary foil 48.
  • Fig. 8 shows a second or bottom view of the body 4A.
  • the first fluid path 16 comprises and is split into a first branch formed by first branch recess 17A and second primary foil 48 and a second branch formed by second branch recess 17B and second primary foil 48.
  • the first branch of the first fluid path feeds first buffer into a first inlet of the sample chamber formed by sample inlet and sample plug.
  • the second branch of the second fluid path feeds first buffer into a second inlet of the sample chamber formed by sample inlet and sample plug.
  • a plurality of sample chamber inlets in the microfluidic test device provides improved flushing of the sample.
  • the sample chamber only has a single inlet.
  • the second fluid path 18 comprises a first branch formed by first branch recess 19A and second primary foil 48 and a second branch formed by second branch recess 19B and second primary foil 48. Liquid from the sample chamber enters the first branch and the second branch of the second fluid path via respective first outlet and second outlet of the sample chamber. The first branch and the second branch of the second fluid path are joined in second fluid path joint 80 before splitting into second primary fluid path 18A and second secondary fluid path 18B.
  • Fig. 9 shows a cut out side view of the microfluidic test device 4A illustrating the heating assembly in further detail.
  • the heating assembly 30 comprises a primary heating element 30A sandwiched between a first electrode layer 90 and a second electrode layer 92 for applying a primary voltage to the primary heating element.
  • the heating assembly 30 (first electrode layer 90) is attached to the second primary foil 48 adjacent to and overlapping the primary and secondary reaction chambers 12, 50.
  • a primary pellet of primary reaction material (not shown) is arranged in the primary reaction chamber, and a secondary pellet 94 of secondary reaction material is arranged in the secondary reaction chamber 50.
  • the thin second primary foil 48 provides a good heat transport to reaction liquid in the reaction chambers 12, 50.
  • Fig. 10 shows an exemplary body 4B of a microfluidic test device.
  • the sample chamber/sample inlet 14A has a single inlet from the first fluid path. Further, the sample chamber/sample inlet 14A has a single outlet to the second fluid path.
  • a single inlet from the first fluid path may be combined with two or more outlets to the second fluid path. Further, two or more inlets from the first fluid path may be combined with a single outlet to the second fluid path.
  • secondary does not denote any order or importance, but rather these terms are used to distinguish one element from another. Note that the words “first”, “second”, “third”, “fourth”, “primary”, and “secondary”, are used here and elsewhere for labelling purposes only and are not intended to denote any specific spatial or temporal ordering. Furthermore, the labelling of a first element does not imply the presence of a second element and vice versa.

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Abstract

A microfluidic test device is disclosed, the microfluidic test device comprising: a body; a first chamber having an outlet provided with a first valve and holding a first buffer having a first buffer volume; a primary reaction chamber; a sample inlet for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device; a first fluid path connecting the outlet of the first chamber and the sample inlet; a second fluid path connecting the sample inlet and the primary reaction chamber; a primary test part comprising a primary test chamber; a third primary fluid path connecting the primary reaction chamber and the primary test part; a primary valve arranged in the third primary fluid path; a flow driving device configured to move fluid from the primary reaction chamber to the primary test part; and a heating assembly configured to heat a reaction fluid in the primary reaction chamber.

Description

MICROFLUIDIC TEST DEVICE
The present disclosure relates to a microfluidic test device, in particular a microfluidic test device for testing body fluids, such as urine and blood.
BACKGROUND
Developments within medical testing has increasingly been focusing on moving testing towards the user, also known as point-of-care-testing (POCT). The traditional diagnosis of e.g. infections typically involves collection of a sample. Most modern laboratories still use traditional testing methods such as cell culture and antigen based detection. The cell culture method is highly specific, but has very low sensitivity, is expensive, slow (takes days) and requires special sample collection, storage, and transport. Immunological assays like the enzyme immunoassay and direct fluorescent antibody (DFA) assay have low sensitivity and specificity as a cell culture method, which limits the use of these tests in diagnostic field.
As an alternative to the traditional laboratory methods, nucleic acid amplification tests (NAATs) were developed allowing detection of e.g. pathogen-specific DNA or RNA sequences. These tests are significantly more sensitive because they can detect as little as single nucleic acid copy of the target.
There are several drawbacks to these types of methods, including that they cannot be used by individuals without expertise within the field or without the use of for example a PGR machine or sample preparation.
However, the complexity of test methods has been and is still setting barriers for their application in POCT.
SUMMARY
It is therefore clear that there is a need for tests that requires little or no sample preparation, a simple test setup, and little or no expertise within the technical field. Such test could for example be an over the counter do-it-yourself kit.
Further, there is a need for providing a microfluidic test device that is easy to use and error-proof.
Accordingly, a microfluidic test device is provided, the microfluidic test device comprising a body; a first chamber having an outlet optionally provided with a first valve and holding a first buffer having a first buffer volume; and a primary reaction chamber. The microfluidic test device comprises a sample inlet for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device; a first fluid path connecting the outlet of the first chamber and the sample inlet; and a second fluid path connecting the sample inlet and the primary reaction chamber. Further, the microfluidic test device comprises a primary test part comprising a primary test chamber; a third primary fluid path connecting the primary reaction chamber and the primary test part; a primary valve arranged in the third primary fluid path; and a flow driving device configured to move fluid from the primary reaction chamber to the primary test part. The microfluidic test device optionally comprises a heating assembly configured to heat a reaction fluid in the primary reaction chamber.
Also disclosed is a microfluidic test system comprising a microfluidic test device as disclosed herein and a sample plug.
It is an important advantage of the present disclosure that complex tests, such as LAMP tests are enabled in a point of care test device. Further, the present disclosure enables error-safe testing by implementation of a plurality of tests in the same device and performed on the same sample.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other features and advantages of the present invention will become readily apparent to those skilled in the art by the following detailed description of exemplary embodiments thereof with reference to the attached drawings, in which : Fig. 1 schematically illustrates an exemplary microfluidic test device,
Fig. 2 is a schematic cross-sectional view of an exemplary microfluidic test device,
Fig. 3 schematically illustrates an exemplary microfluidic test device,
Fig. 4 is a perspective view of exemplary microfluidic test device,
Fig. 5 is another perspective view of exemplary microfluidic test device,
Fig. 6 is a perspective view of exemplary body of microfluidic test device,
Fig. 7 is another perspective view of exemplary body of microfluidic test device,
Fig. 8 is a second (bottom) view of exemplary body of microfluidic test device,
Fig. 9 is a cut out view of exemplary microfluidic test device,
Fig. 10 is a second (bottom) view of exemplary body of microfluidic test device, DETAILED DESCRIPTION
Various exemplary embodiments and details are described hereinafter, with reference to the figures when relevant. It should be noted that the figures may or may not be drawn to scale and that elements of similar structures or functions are represented by like reference numerals throughout the figures. It should also be noted that the figures are only intended to facilitate the description of the embodiments. They are not intended as an exhaustive description of the invention or as a limitation on the scope of the invention. In addition, an illustrated embodiment needs not have all the aspects or advantages shown. An aspect or an advantage described in conjunction with a particular embodiment is not necessarily limited to that embodiment and can be practiced in any other embodiments even if not so illustrated, or if not so explicitly described.
The microfluidic test device may be a point-of-care (POC) microfluidic test device. Point-of-care testing (POCT), or bedside testing is defined as medical diagnostic testing at or near the point of care - that is, at the time and place of patient care. This contrasts with the historical pattern in which testing was wholly or mostly confined to the medical laboratory, which entailed sending off specimens away from the point of care and then waiting hours or days to learn the results, during which time care must continue without the desired information. Point-of-care tests are simple medical tests that can be performed at the bedside.
The microfluidic test device may comprise a housing, wherein the body, e.g . with foils, is accommodated within the housing. The housing may have one or more openings to allow access to the inside of the housing, e.g. to the sample inlet. One or more button members may be included in the housing. A first button of the housing may be associated with the first chamber and/or a second button of the housing may be associated with the flow driving device.
The microfluidic test device comprises a body. The body may be an elongated body having a first end and a second end. The body may have a first end surface and/or a second end surface. The body may have one or more first surfaces, e.g. a first primary surface and/or a first secondary surface, and one or more second surface(s). The first surface(s) may be intended for facing upwards when the microfluidic test device is positioned in a test position. The second surface(s) may be intended for facing downwards when the microfluidic test device is positioned in a test position. The body may comprise one or more grooves or recesses, also denoted first groove(s), in the first surface(s). The body may comprise one or more grooves or recesses, also denoted second groove(s), in the second surface(s). The first and/or second grooves may form at least a part of the fluid paths of the microfluidic test device. The body may have one or more through-going bores from first surface(s) to second surface(s). The body one or more through-going bores may form at least a part of the fluid paths of the microfluidic test device.
The body may be made of a body material. The body material may be glass, silicon, or a polymer, such as Polydimethylsiloxane (PDMS). In one or more exemplary microfluidic test devices, the body is made of polypropylene (PP). The body material may be black or grey. A black or grey PP body material is cheap and has good laser welding properties, in turn reducing welding time.
The microfluidic test device may comprise one or more first foils, such as a first primary foil and/or a first secondary foil, attached to the first surface(s) of the body. The microfluidic test device may comprise one or more second foils, such as a second primary foil and/or a second secondary foil, on the second surface(s) of the body. The first foil(s) and/or the second foil(s) may be attached to the body by laser welding. The first foil(s) may have a thickness in the range from 0.05 mm to 2 mm, such as from 0.2 mm to 0.8 mm . The second foil(s) may have a thickness in the range from 0.05 mm to 2 mm, such as from 0.2 mm to 1.0 mm .
A foil, such as one or more first foils and/or one or more second foil(s) may be made of a flexible material.
The microfluidic test device may comprise a first primary foil attached to the first primary surface of the body. The first primary foil may be made of a first primary foil material. The first primary foil material may be the same as the body material, e.g. to facilitate attachment of the first primary foil to the body. The first primary foil material may be a polymer, such as Polydimethylsiloxane (PDMS). In one or more exemplary microfluidic test devices, the first primary foil is made of polypropylene (PP). The first primary foil material may be transparent. A transparent first primary foil material allows a user to inspect or follow liquid flow in fluid paths partly formed by the first primary foil. Further, a user can read test results through a transparent first primary foil material covering and/or sealing one or more openings in the body.
The microfluidic test device may comprise a first secondary foil attached to the first secondary surface of the body. The first secondary foil may be made of a first secondary foil material. The first secondary foil material may be metal material or an alloy. In one or more exemplary microfluidic test devices, the first secondary foil is made of aluminium. The microfluidic test device may comprise a second primary foil attached to the second surface of the body. The second primary foil may be made of a second primary foil material. The second primary foil material may be the same as the body material, e.g. to facilitate attachment of the second primary foil to the body. The second primary foil material may be a polymer, such as Polydimethylsiloxane (PDMS). In one or more exemplary microfluidic test devices, the second primary foil is made of polypropylene (PP). The second primary foil material may be transparent. A transparent second primary foil material allows a user to inspect or follow liquid flow in fluid paths partly formed by the second primary foil.
The microfluidic test device comprises a first chamber having an outlet and holding a first buffer having a first buffer volume. The outlet of the first chamber may be provided with a first valve. The first valve may be configured to open when the pressure on the inlet side of the first valve is larger than a first pressure threshold. The first chamber may have a first volume in the range from 10 microliters to 900 microliters. In one or more exemplary microfluidic test devices, the first chamber has a first volume in the range from 30 microliters to 1,000 microliters, such as 300 microliters, 400 microliters, 500 microliters, or 600 microliters, 700 microliters, 800 microliters, 900 microliters, or any ranges therebetween.
The first buffer may comprise components useful in amplifying a nucleotide target in the sample. In one embodiment, such amplification is provided by Loop-mediated isothermal amplification (LAMP). In LAMP, the target sequence is amplified at a constant temperature typically 60-65 °C using either two or three sets of primers and a polymerase with high strand displacement activity in addition to a replication activity. Typically, 4 different primers are used to identify 6 distinct regions on the target gene, which adds highly to the specificity. An additional pair of "loop primers" can further accelerate the reaction. Due to the specific nature of the action of these primers, the amount of DNA produced in LAMP is considerably higher than PCR based amplification.
The first buffer optionally comprises a neutral chemical compound with a positively charged cationic functional group such as a quaternary ammonium or phosphonium cation (generally: onium ions) which bears no hydrogen atom and optionally with a negatively charged functional group such as a carboxylate group which may not be adjacent to the cationic site. The neutral chemical compound may be Betaine.
The first buffer optionally comprises one or more inorganic salts, such as but not limited to MgS04 and/or (NH4)2S04. The microfluidic test device comprises one or more reaction chambers including a primary reaction chamber. The primary reaction chamber may have a volume larger than 20 microliters and/or less than 500 microliters. In one or more exemplary microfluidic test devices, the primary reaction chamber may have a volume in the range from 40 microliters to 200 microliters, such as 50 microliters, 75 microliters, 100 microliters, 125 microliters, 150 microliters, 175 microliters, or any ranges therebetween. The microfluidic test device may comprise a primary reaction chamber plug forming a part of the primary reaction chamber. A microfluidic test device with reaction chamber plugs facilitates positioning of reaction material in reaction chamber(s). For example, a pellet with reaction material, such as a primary pellet with primary reaction material may be placed in a primary reaction chamber body part followed by a closing of the primary reaction chamber with a primary reaction chamber plug.
The microfluidic test device may comprise reaction material arranged or deposited at different positions in the microfluidic test device.
The microfluidic test device may comprise a primary reaction material. The primary reaction material may be arranged in the primary reaction chamber.
The primary reaction material optionally comprises short strands of RNA and/or DNA (generally about 18-22 bases) that serve as a starting point for DNA synthesis.
In one or more exemplary microfluidic test devices, the primary reaction material comprises nucleoside triphosphate (NTP).
In one or more exemplary microfluidic test devices, the primary reaction material comprises an enzyme capable of synthesising chains or polymers of nucleic acids, optionally in combination with NTP and/or short strands of RNA and/or DNA. The enzyme capable of synthesising chains or polymers of nucleic acids may be a LAMP polymerase.
The primary reaction material may be subjected to a freeze-drying process to protect the reagents and ensure the stability and re-suspendability properties of the reagent(s) prior to the introduction of the reagent into the primary reaction chamber. Thus, in one or more exemplary microfluidic test devices, the primary reaction material is in a dry and/or pellet like form .
The primary reaction material may be coated onto a surface of the body and/or a foil of the microfluidic test device. The microfluidic test device comprises a sample inlet for receiving a sample. The sample inlet is configured for feeding a sample having a sample volume, into the medical test device.
The microfluidic test device comprises a first fluid path. The first fluid path may connect the outlet of the first chamber and the sample inlet. The first fluid path may comprise a first branch and a second branch in parallel to the first branch. The first branch of the first fluid path may be connected to a first inlet of sample chamber formed by sample inlet and sample plug. Thus, the first branch may feed first buffer into the sample chamber via first inlet. The second branch of the second fluid path may be connected to a second inlet of sample chamber formed by sample inlet and sample plug. Thus, the second branch of the first fluid path may feed first buffer into the sample chamber via second inlet. A plurality of branches in the first fluid path, the branches connected to respective sample chamber inlets in the microfluidic test device provides improved flushing of the sample. In one or more exemplary microfluidic test devices, the sample chamber only has a single inlet.
The microfluidic test device comprises a second fluid path. The second fluid path may connect the sample inlet and the primary reaction chamber. The second fluid path may comprise a first branch and a second branch in parallel to the first branch. The first branch and the second branch of the second fluid path are optionally connected to respective first outlet and second outlet of the sample chamber. Thus, liquid from the sample chamber may enter the first branch and the second branch of the second fluid path via respective first outlet and second outlet of the sample chamber. The first branch and the second branch of the second fluid path may be joined in second fluid path joint to a single fluid path part, optionally before splitting into second primary fluid path and second secondary fluid path. In one or more exemplary microfluidic test devices, the second primary fluid path is directly connected to first outlet of sample chamber and the second secondary fluid path is directly connected to the second outlet of sample chamber. In one or more exemplary microfluidic test devices, the sample chamber only has a single outlet that may later be branched into second primary fluid path and second secondary fluid path.
The microfluidic test device comprises a primary test part comprising a primary test chamber.
The microfluidic test device comprises a third primary fluid path optionally connecting the primary reaction chamber and the primary test part. The microfluidic test device may comprise a primary valve arranged in the third primary fluid path. The primary valve acts as a blocking mechanism to separate the primary test part and liquid (sample, first buffer and reaction material) during a reaction time. The primary valve may be configured to open when the pressure on the inlet side of the primary valve is larger than a primary pressure threshold.
The microfluidic test device comprises a flow driving device configured to move fluid (primary test liquid) from the primary reaction chamber to the primary test part. Thus, a user operating the flow driving device may be able to break or force primary valve to open.
The microfluidic test device optionally comprises a heating assembly configured to heat a (primary) reaction fluid in the primary reaction chamber.
The heating assembly may be configured to heat the (primary) reaction fluid in the primary reaction chamber to a primary reaction temperature in the range from 30°C to 100°C, preferably in the range from 30°C to 70°C, such as in the range from 45°C to 68°C. In one or more exemplary microfluidic test devices, the primary reaction temperature is in the range from 55°C to 65°C, such as from 58°C to 63°C. In one or more exemplary microfluidic test devices, the primary reaction temperature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C.
The heating assembly may comprise one or more heating elements, such as one or more primary heating elements, e.g. for heating the primary reaction chamber.
The heating assembly may comprise a primary heating element adjacent the primary reaction chamber.
The primary heating element may be configured to self-regulate to a primary temperature, e.g. upon application of a primary voltage. The primary temperature may be in the range from 30°C to 100°C, preferably in the range from 30°C to 80°C, such as in the range from 45°C to 75°C. In one or more exemplary microfluidic test devices, the primary temperature is in the range from 55°C to 70°C, such as from 58°C to 67°C. In one or more exemplary microfluidic test devices, the primary temperature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C. In one or more exemplary microfluidic test devices, the primary voltage is in the range from 0.5V to 5V, such as in the range from 1.5V to 3.5 V, e.g. 3V A self- regulating primary heating element reduces or eliminates the need for electrical control circuitry, in turn providing a simple temperature control. The microflu idic test device may comprise a first terminal and a second terminal . The primary heating element may be connected to the first term inal (first side and/or first end of primary heating element) and the second terminal (second side and/or second) end of primary heating element) for applying a voltage to the heating assembly, such as the primary heating element.
The heating assembly, e.g . when configured for two-reaction cham ber heating, may have a length in the range from 15 mm to 50 mm, such as from 20 m m to 30 mm m e.g . 24 mm . The heating assem bly, e.g . when configured for two-reaction cham ber heating, may have a width in the range from 5 m m to 30 m m, such as from 10 mm to 20 mm m e.g . 11 m m . The heating assembly may have a thickness in the range from 0.2 mm to 3 m m .
The heating assembly may comprise a first electrode layer arranged on a first side of the primary heating element. The heating assem bly may com prise a second electrode layer arranged on a second side of the primary heating element. Thus, the primary heating element may be sandwiched between the first electrode layer and second electrode layer for applying a primary voltage to the primary heating element. The first electrode layer (and thus the primary heating element) and second electrode layer (and thus the primary heating element) may be respectively connected to first term ina l and second term ina l. The first terminal and the second term inal may be arranged in a battery docket of the microflu idic test device. The first term inal and the second terminal may be arranged in a connector for connecting an external power sou rce to the m icrofluidic test device. The first electrode layer and/or the second electrode layer may be made of a su itable electrode material, such as copper, nickel or an alloy com prising copper and/or nickel .
The heating assembly, e.g . first electrode layer of the heating assembly, may be attached to the second primary foil, e.g . by glu ing . The heating assem bly may be adjacent to and/or overlapping the primary and secondary reaction chambers.
The primary heating element may com prise a resin material and/or one or more polymers. The primary heating element may com prise a carbon-based heater resin . The primary heating element may be made of a material with positive tem perature coefficient of resistance. The primary heating element may com prise a ceramic element, such as a positive temperatu re coefficient (PCT) ceram ic. The ceramic element may be made of, based on, or com prise bariu m titanate (BaTiOS).
In one or more exemplary m icrofluidic test devices, the microfluidic test device com prises a secondary reaction chamber. The secondary reaction chamber may have a volume larger than 20 microliters and/or less than 500 microliters. In one or more exemplary microfluidic test devices, the secondary reaction chamber may have a volume in the range from 40 microliters to 200 microliters, such as 50 microliters, 75 microliters, 100 microliters, 125 microliters, 150 microliters, 175 microliters, or any ranges therebetween. The microfluidic test device may comprise a secondary reaction chamber plug forming a part of the secondary reaction chamber.
The second fluid path may connect the sample inlet and the secondary reaction chamber. For example, the second fluid path may be Y-shaped with a first end connected to the sample inlet, a primary second end connected to the primary test part, and a secondary second end connected to the secondary reaction chamber.
The microfluidic test device may comprise a secondary test part comprising a secondary test chamber.
The microfluidic test device may comprise a third secondary fluid path connecting the secondary test part and one or more reaction chambers, such as the primary reaction chamber and/or the secondary reaction chamber. The microfluidic test device may comprise a secondary valve arranged in the third secondary fluid path. The flow driving device may be configured to move fluid from the primary reaction chamber to the secondary test part. The flow driving device may be configured to move fluid from the secondary reaction chamber to the secondary test part.
The secondary valve acts as a blocking mechanism to separate the secondary test part and liquid (sample, first buffer and reaction material) during a reaction time. The secondary valve may be configured to open when the pressure on the inlet side of the secondary valve is larger than a secondary pressure threshold. Thus, a user operating the flow driving device may be able to break or force secondary valve to open.
The microfluidic test device may comprise a secondary reaction material. The secondary reaction material may be arranged in the secondary reaction chamber. The secondary reaction material may be the same as or different from the first reaction material.
The secondary reaction material optionally comprises short strands of RNA and/or DNA (generally about 18-22 bases) that serve as a starting point for DNA synthesis.
In one or more exemplary microfluidic test devices, the secondary reaction material comprises nucleoside triphosphate (NTP).
In one or more exemplary microfluidic test devices, the secondary reaction material comprises an enzyme capable of synthesising chains or polymers of nucleic acids, optionally in com bination with NTP and/or short strands of RNA and/or DNA. The enzyme capable of synthesising chains or polymers of nucleic acids may be a LAMP polymerase.
The seconda ry reaction material may be su bjected to a freeze-drying process to protect the reagents and ensure the stability and re-suspendability properties of the reagent(s) prior to the introduction of the reagent into the secondary reaction cham ber. Thus, in one or more exemplary microfluidic test devices, the secondary reaction material is in a dry and/or pellet like form .
The heating assembly may be configured to heat a (secondary) reaction flu id in the secondary reaction chamber to a secondary reaction tem perature in the range from 30°C to 100°C, preferably in the range from 30°C to 70°C, such as in the range from 45°C to 68°C. In one or more exem plary m icrofluidic test devices, the secondary reaction temperature is in the range from 55°C to 65°C, such as from 58°C to 63°C. In one or more exemplary m icrofluidic test devices, the secondary reaction
tem perature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C.
The first primary heating element may be configured to heat the secondary reaction cham ber. The heating assembly may com prise one or more heating elements, such as one or more secondary heating elements, e.g . for heating the secondary reaction cham ber. The heating assem bly may com prise a seconda ry heating element adjacent the secondary reaction chamber. The primary heating element may be adjacent the secondary reaction chamber.
The seconda ry heating element may com prise a resin material and/or one or more polymers. The secondary heating element may com prise a carbon-based heater resin. The secondary heating element may be made of a material with positive temperatu re coefficient of resistance. The secondary heating element may comprise a ceram ic element, such as a positive temperatu re coefficient (PCT) ceram ic. The ceramic element may be made of, based on, or com prise bariu m titanate (BaTiOS).
The secondary heating element may be configured to self-regu late to a secondary tem perature, e.g . u pon application of a secondary voltage. The secondary
tem perature may be the same as or different from the primary temperatu re. The secondary tem perature may be in the range from 30°C to 100°C, preferably in the range from 30°C to 80°C, such as in the range from 45°C to 75°C. In one or more exem plary m icroflu idic test devices, the primary temperatu re is in the range from 55°C to 70°C, such as from 58°C to 67°C. In one or more exem plary m icrofluidic test devices, the primary temperature is 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C and/or 65°C. In one or more exemplary microfluidic test devices, the secondary voltage is the same as or different from the primary voltage. The secondary voltage may be in the range from 0.5V to 5V, such as in the range from 1.5V to 3.5 V, such as 3V. A self-regulating primary heating element reduces or eliminates the need for electrical control circuitry, in turn providing a simple temperature control. Thus, the microfluidic test device enables different tests with different test temperatures in the same microfluidic test device. Primary and/ secondary voltages less than 5V may be advantageous for a POCT device, e.g. for a battery-driven POCT device.
The flow driving device may comprise a second chamber having an outlet optionally provided with a second valve, wherein the outlet of the second chamber is connected to the first fluid path or the second fluid path. The second valve may be configured to open when the pressure on the inlet side of the second valve is larger than a second pressure threshold. Thus, the microfluidic test device may comprise a fourth fluid path connecting the outlet of the second chamber and the first fluid path or the second fluid path. In one or more exemplary microfluidic test devices, the second chamber has a second volume in the range from 30 microliters to 2,000 microliters, such as 300 microliters, 400 microliters, 500 microliters, 600 microliters, 800 microliters, 1,000 microliters, 1,20 microliters, 1,400 microliters, 1,600 microliters, 1,800 microliters, or any ranges therebetween. The microfluidic test device may comprise a second fluid, such as air and/or liquid in the second chamber.
The microfluidic test system may comprise a seal covering the sample inlet. The seal may be peeled off, removed or broken prior to or just prior to testing by inserting a sample plug into the microfluidic test device. Thus, the risk of contaminating the inside of the microfluidic test device may be reduced.
A test part of the microfluidic test device, such as the primary test part and/or the secondary test part may comprise a second lateral flow strip. Thus, the primary test part may comprise a first lateral flow strip having a first end connected to or inserted into an outlet of the primary test chamber. The secondary test part may comprise a second lateral flow strip having a first end connected to or inserted into an outlet of the secondary test chamber. A plurality of lateral flow strips enables detection of faulty tests and/or enables performance of different tests on a single sample. The first lateral flow strip may have a length in the range from 30 mm to 100 mm, such as in the range from 40 to 80 mm. In one or more exemplary microfluidic test devices, the first lateral flow strip has a length in the range from 60 mm to 70 mm .
The first lateral flow strip may have a width in the range from 1 mm to 10 mm, such as in the range from 1.5 mm to 4.0 mm. Narrow lateral flow strips have reduced requirements for liquid volume. In one or more exemplary microfluidic test devices, the first lateral flow strip has a width in the range from 2.0 mm to 3.5 mm, such as 3.0 mm .
The second lateral flow strip may have a length in the range from 30 mm to 100 mm, such as in the range from 40 to 80 mm. In one or more exemplary microfluidic test devices, the second lateral flow strip has a length in the range from 60 mm to 70 mm.
The second lateral flow strip may have a width in the range from 1 mm to 10 mm, such as in the range from 1.5 mm to 4.0 mm. Narrow lateral flow strips have reduced requirements for liquid volume. In one or more exemplary microfluidic test devices, the second lateral flow strip has a width in the range from 2.0 mm to 3.5 mm, such as 3.0 mm .
Lateral flow strips in the present context are simple devices intended to detect the presence (or absence) of a target analyte in sample (matrix) without the need for specialized and costly equipment.
Typically, these tests are used for medical diagnostics either for home testing, point of care testing, or laboratory use. A widely spread and well known application is the home pregnancy test.
The technology is based on a series of capillary beds, such as pieces of porous paper or sintered polymer. Each of these elements has the capacity to transport fluid (e.g., urine) spontaneously. The first element (the sample pad) acts as a sponge and holds an excess of sample fluid. Once soaked, the fluid migrates to the second element (conjugate pad) in which the manufacturer has stored the so-called conjugate, a dried format of bio-active particles in a salt-sugar matrix that contains everything to guarantee an optimized chemical reaction between the target molecule and its chemical partner that has been immobilized on the particle's surface.
While the sample fluid dissolves the salt-sugar matrix, it also dissolves the particles and in one combined transport action the sample and conjugate mix while flowing through the porous structure. In this way, the analyte binds to the particles while migrating further through the third capillary bed. This material has one or more areas (often called stripes) where a third molecule has been immobilized by the manufacturer. By the time the sample- conjugate mix reaches these strips, analyte has been bound on the particle and the third 'capture' molecule binds the complex. After a while, when more and more fluid has passed the stripes, particles accumulate and the stripe-area typically changes color.
Lateral flow strip based signal visualization and enhancement is very beneficial on cost perspective, this is presumably the cheapest solution to form simple optical readout that is applicable for point-of-care devices.
While using lateral flow strips for amplicon detection and signal visualization one should also bear in mind that upstream components, including those that are coming from sample matrix, will not inhibit the very binding reaction on lateral flow. This also usually requires balancing of lateral flow buffer and amount of e.g. conjugated gold nanoparticles that are required. Wrong balancing of components will result in signal loss or in nonspecific signals.
Different haptens can be used for the labelling of the primers, including FAM, biotin, DIG, to detect amplification product with lateral flow strips. Using different hapten combination multiple product detection can be achieved (multiplex reaction detecting several different pathogens at once).
The body may comprise a first valve body part forming a part of the first valve. The first valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
The body may comprise a second valve body part forming a part of the second valve. The second valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
The body may comprise a primary valve body part forming a part of the primary valve. The primary valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
The body may comprise a secondary valve body part forming a part of the secondary valve. The secondary valve body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body. The body may comprise a primary test chamber body part forming a part of the primary test chamber. The primary test chamber body part may be formed as a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
The body may comprise a secondary test chamber body part forming a part of the secondary test chamber. The secondary test chamber body part may be formed as a recess in a recess in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
The body/microfluidic test device may comprise a first flow strip chamber and/or a second flow strip chamber. The first flow strip chamber may be accessible, e.g. for reading test results, through a first opening in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body. The second flow strip chamber may be accessible, e.g. for reading test results, through a second opening 70 in a surface of the body, such as a first primary surface, a first secondary surface or a second surface of the body.
The body may comprise one or more holding elements for holding and/or fixate lateral flow strip(s) in position, e.g. between the body and a second foil, such as a second primary foil. The body may comprise one or more first holding elements, such as a first primary holding element and/or a first secondary holding element, in the first flow strip chamber, optionally configured to hold or fixate a first lateral flow strip in position between the body and the second primary foil. The body may comprise one or more second holding elements, such as a second primary holding element and/or a second secondary holding element, in the second flow strip chamber, optionally configured to hold or fixate a second lateral flow strip in position between the body and the second primary foil.
The first primary foil may comprise a primary valve foil part forming a part of the primary valve. The first primary foil may comprise a secondary valve foil part forming a part of the secondary valve. The first primary foil may comprise a first primary test chamber foil part forming a part (top) of the primary test chamber. The first primary foil may comprise a first secondary test chamber foil part forming a part (top) of the secondary test chamber. The first primary foil may cover and/or seal the first opening in the body. The first primary foil may cover and/or seal the second opening in the body. The first secondary foil may comprise a first chamber foil part forming a part of the first chamber. The first secondary foil may comprise a second chamber foil part forming a part of the second chamber.
The first secondary foil may comprise a first valve foil part forming a part of the first valve. The first secondary foil may comprise a second valve foil part forming a part of the second valve.
The first primary foil and the first secondary foil may be made of different materials, e.g. to implement different functions in the microfluidic test device.
The second primary foil may comprise a second primary test chamber foil part forming a part (bottom) of the primary test chamber. The second primary foil may comprise a second secondary test chamber foil part forming a part (bottom) of the secondary test chamber.
The second primary foil may comprise a primary reaction chamber foil part forming a part (bottom) of the primary reaction chamber. The second primary foil may comprise a secondary reaction chamber foil part forming a part (bottom) of the secondary reaction chamber. The heating assembly may be attached to the second primary foil. The heating assembly may partly or fully cover the primary reaction chamber foil part and/or the secondary reaction chamber foil part. Thus, efficient heat transfer to the reaction chambers are provided for.
The second primary foil may comprise a sample inlet foil part forming a part (bottom) of the sample inlet.
The second primary foil may comprise a first flow strip chamber foil part forming a part of the first flow strip chamber and/or a second flow strip chamber foil part forming a part of the second flow strip chamber.
The second primary foil may form a part of one or more fluid paths, such as the first, second, third (primary and secondary), and/or fourth fluid paths.
Turning now to the figures, Fig. 1 schematically illustrates a first (top) view of an exemplary microfluidic test device. The microfluidic test device 2 comprises a body 4 and a first chamber 6 having an outlet 8 provided with a first valve 10 and holding a first buffer having a first buffer volume.
The microfluidic test device 2 comprises a primary reaction chamber 12 and a sample inlet 14 for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device 2. A first fluid path 16 connects the outlet 8 of the first chamber 6 and the sample inlet 14 and a second fluid path 18 connects the sample inlet 14 and the primary reaction chamber 12. Further, the microfluidic test device 2 comprises a primary test part 20 comprising a primary test chamber 22 with a third primary fluid path 24 connecting the primary reaction chamber 12 and the primary test part 20. A primary valve 26 is arranged in the third primary fluid path 24. The microfluidic test device 2 comprises a flow driving device 28 configured to move fluid from the primary reaction chamber 12 to the primary test part 20. The flow driving device 28 comprises a second chamber 28A having an outlet optionally provided with a second valve 28B. The outlet of the second chamber is connected to the first fluid path 16 via fourth fluid path 29.
The microfluidic test device 2 comprises a heating assembly 30 configured to heat a reaction liquid in the primary reaction chamber 12. The heating assembly 30 is connected to a power source (not shown). The power source may be one or more batteries accommodated or inserted in the microfluidic test device. The power source may be an external power source connected to the microfluidic test device via a connector (not shown).
The primary test part 20 comprises a first lateral flow strip 32 having a first end 34 connected to an outlet of the primary test chamber 22. The first lateral flow strip 32 has a length of 65 mm and a width of 3.0 mm.
Fig. 2 shows an exemplary cross-sectional view of the microfluidic test device 2. The microfluidic test device 2. The body 4 has a first end 36 with a first end surface, and a second end 38 with a second end surface. The body 4 has a first surface 40 intended for facing upwards when the microfluidic test device is positioned in a test position, and a second surface 42 opposite the first surface 40 and intended for facing downwards when the microfluidic test device is positioned in a test position.
The microfluidic test device comprises a first primary foil 44 attached to the first surface 40 of the body 4. The first primary foil 44 forms a part of the third primary fluid path 24 and the primary valve 26.
The microfluidic test device comprises a first secondary foil 46 attached to the first surface 40 of the body 4. The first secondary foil 46 forms a part of the first chamber 6 and the first valve 10.
The microfluidic test device comprises a first tertiary foil 47 attached to the first surface 40 of the body 4. The first tertiary foil 47 forms a part of the flow driving device 28. The flow driving device 28 is embodied as a second chamber with an outlet and a second valve arranged at the outlet of the second chamber. The microfluidic test device comprises a second primary foil 48 attached to the second surface 42 of the body 4.
The first fluid path 16 connects the first chamber 6 and the bottom of sample inlet 14. The second fluid path 18 connects the sample inlet 14 and the first reaction chamber 12. Thus, first buffer can be moved from the first chamber 6 through the first fluid path 16 into the sample inlet 14 by pressing on the first secondary foil 46 with a force sufficient to open the first valve 10, i.e. a force to apply a first pressure larger than the first pressure threshold. The first buffer thus flushes sample in the sample inlet 14 through the second fluid path 18 and into the first reaction chamber 12, where the first buffer, the sample and a primary reaction material are mixed. After a reaction, assisted by heating with heating assembly 30, has taken place, the flow driving device 28 is activated by pressing on the first tertiary foil 47 with a force sufficient to open the second valve 28B, i.e. a force to apply a second pressure larger than the second pressure threshold. Thereby, primary reaction liquid in the primary reaction chamber 12 is moved into the primary test chamber 22 via the third primary fluid path 24 by the primary valve 26 opening upon activation of the flow driving device 28. The primary test liquid in the primary test chamber 22 flows into the first lateral flow strip 32 for obtaining a readout of the test result.
Fig. 3 schematically illustrates a first (top) view of an exemplary microfluidic test device. The microfluidic test device 2A comprises a body 4 and a first chamber 6 having an outlet 8 provided with a first valve 10 and holding a first buffer having a first buffer volume.
The microfluidic test device 2 comprises a primary reaction chamber 12 and a sample inlet 14 for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device 2. A first fluid path 16 connects the outlet 8 of the first chamber 6 and the sample inlet 14 and a second fluid path 18 connects the sample inlet 14 and the primary reaction chamber 12. Further, the microfluidic test device 2 comprises a primary test part 20 comprising a primary test chamber 22 with a third primary fluid path 24 connecting the primary reaction chamber 12 and the primary test part 20. A primary valve 26 is arranged in the third primary fluid path 24. The microfluidic test device 2 comprises a flow driving device 28 configured to move fluid from the primary reaction chamber 12 to the primary test part 20, and a heating assembly 30 configured to heat a reaction fluid in the primary reaction chamber 12.
The primary test part 20 comprises a first lateral flow strip 32 having a first end 34 connected to an outlet of the primary test chamber 22. Further, the microfluidic test device 2A comprises a secondary reaction chamber 50, wherein the second fluid path 18 connects the sample inlet 14 and the secondary reaction chamber 50. Further, the microfluidic test device 2A comprises a secondary test part 52 comprising a secondary test chamber 54 with a third secondary fluid path 56 connecting the secondary reaction chamber 50 and the secondary test part 52. A secondary valve 58 is arranged in the third secondary fluid path 56. The flow driving device 28 is configured to move fluid from the secondary reaction chamber 50 to the secondary test part 52, and the heating assembly 30 is optionally configured to heat a reaction fluid in the secondary reaction chamber 50. The secondary test part 52 comprises a second lateral flow strip 60 having a first end 62 connected to an outlet of the secondary test chamber 54. The second lateral flow strip 60 has a length of 65 mm and a width of 3.0 mm .
Figs. 4-10 show different views of exemplary microfluidic test system(s) and parts thereof. The microfluidic test system comprises a microfluidic test device (housing not shown) and a sample plug.
Figs. 4 and 5 show perspective views of parts of microfluidic test device 2B with a sample plug 63 inserted in the sample inlet of the microfluidic test device. The microfluidic test device 2B comprises a body 4A and one or more foils attached to surfaces of the body. The microfluidic test device 2B comprises a first primary foil 44 attached to a first primary surface 40A of the body 4A and forming a part of the third fluid paths (primary and secondary), the primary valve, and the secondary valve of the microfluidic test device 2B. The first primary foil 44 optionally is a flexible plastic foil made of polypropylene that has been laser-welded to the body 4A made of polypropylene. The microfluidic test device 2B comprises a first secondary foil 46 attached to a first secondary surface 40B (See Fig. 6) of the body 4A and forming a part of the first chamber 6, first valve 10, second chamber 28A, and second valve 28B. The first secondary foil 46 optionally is a metal foil, such as an aluminium foil, and/or comprises one or more metal layers.
The first surfaces 40A, 40B are intended for facing upwards when the microfluidic test device 2B is positioned in a test position, and the second surface 42 is intended for facing downwards when the microfluidic test device 2B is positioned in a test position.
The microfluidic test device 2B comprises a second primary foil 48 attached to the second surface 42 (See Fig. 7) of the body 4A. Further, the microfluidic test device 2B comprises a heating assembly 30 comprising a primary heating element. The heating element is arranged on the second primary foil 48 adjacent the primary reaction chamber and the secondary reaction chamber and configured to heat the primary reaction chamber (and primary reaction liquid) and the secondary reaction chamber (and secondary reaction liquid). The second primary foil 48 forms a part of the first, second, third (primary and secondary), and fourth fluid paths, primary reaction chamber, secondary reaction chamber, primary test chamber, secondary test chamber, and sample inlet (sample chamber).
The microfluidic test device 2B comprises a primary reaction chamber 12 and a sample inlet 14 for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device 2B. The microfluidic test device 2B comprises a primary reaction chamber plug 12A forming a part of the primary reaction chamber 12. The sample inlet 14 is configured for receiving the sample plug 63, the sample plug 63 carrying the sample. A first fluid path connects the outlet of the first chamber 6 and the sample inlet 14 and a second fluid path connects the sample inlet 14 and the primary reaction chamber 12. Further, the microfluidic test device 2B comprises a primary test part comprising a primary test chamber and a first lateral flow strip with a third primary fluid path connecting the primary reaction chamber 12 and the primary test part (primary test chamber). A primary valve is arranged in the third primary fluid path. The microfluidic test device 2B comprises a flow driving device 28 configured to move fluid from the primary reaction chamber 12 to the primary test part. The flow driving device 28 comprises a second chamber 28A having an outlet optionally provided with a second valve. The outlet of the second chamber is connected to the first fluid path via fourth fluid path.
Further, the microfluidic test device 2B comprises a secondary reaction chamber 50, wherein the second fluid path connects the sample inlet 14 and the secondary reaction chamber 50. The microfluidic test device 2B comprises a secondary reaction chamber plug 50A forming a part of the secondary reaction chamber 50. Further, the microfluidic test device 2B comprises a secondary test part comprising a secondary test chamber and a second lateral flow strip, with a third secondary fluid path connecting the secondary reaction chamber 50 and the secondary test part
(secondary test chamber). A secondary valve is arranged in the third secondary fluid path. The flow driving device 28 is configured to move fluid from the secondary reaction chamber 50 to the secondary test part.
Fig. 6 shows a perspective view of a body of the microfluidic test device.
A first valve body part 10A of the body 4A forms a part of the first valve 10. The first valve body part 10A is formed as a recess in the first secondary surface 40B of the body 4A. A first through-going bore 16A from the first secondary surface 40B to the second surface 42 forms a part of the first fluid path 18.
A primary reaction chamber body part 12B forms a part of the primary reaction chamber 12. The primary reaction chamber body part 12B is formed as a through- going bore in the body with the primary reaction chamber plug 12A and the second primary foil 48 forming top and bottom of the primary reaction chamber 12.
A primary test chamber body part 22A of the body 4A forms a part of the primary test chamber 22. The primary test chamber body part 22A is formed as a through-going bore from the first primary surface 40A to the second surface 42. The first primary foil 44 and the second primary foil 48 form top and bottom of the primary test chamber 22.
A primary valve body part 26A of the body 4A forms a part of the primary valve 26. The primary valve body part 26A is formed as a recess in the first primary surface 40A of the body 4A. A primary through-going bore 24A from the first primary surface 40A to the second surface 42 forms a part of the third primary fluid path 24.
A second valve body part 28C of the body 4A forms a part of the second valve 28B. The second valve body part 28C is formed as a recess in the first secondary surface 40B of the body 4A. A fourth through-going bore 29A from the first secondary surface 40B to the second surface 42 forms a part of the fourth fluid path 29.
A secondary reaction chamber body part 50B forms a part of the secondary reaction chamber 50. The secondary reaction chamber body part 50B is formed as a through- going bore in the body with the secondary reaction chamber plug 50A and the second primary foil 48 forming top and bottom of the secondary reaction chamber 50.
A secondary test chamber body part 54A of the body 4A forms a part of the secondary test chamber 54. The secondary test chamber body part 54A is formed as a through- going bore from the first primary surface 40A to the second surface 42. The first primary foil 44 and the second primary foil 48 form top and bottom of the secondary test chamber 54.
A secondary valve body part 58A of the body 4A forms a part of the secondary valve 58. The secondary valve body part 58A is formed as a recess in the first primary surface 40A of the body 4A. A secondary through-going bore 56A from the first primary surface 40A to the second surface 42 forms a part of the third secondary fluid path 56. The microfluidic test device comprises a first flow strip chamber and a second flow strip chamber partly formed in the body 4A. The first flow strip chamber is accessible through a first opening 68 in the first primary surface 40A, and the second flow strip chamber is accessible through a second opening 70 in the first primary surface 40A. The first and second openings enables optical readout of lateral flow strips.
Fig. 7 shows another perspective view of the body 4A, where a first recess 16B forms a part of the first fluid path 16 between the first chamber 6 and the sample inlet 14 partly formed by sample inlet body part 14A. The second fluid path comprises a second primary fluid path 18A and a second secondary fluid path 18B. The second primary fluid path 18A connects the sample inlet 14 and the primary reaction chamber 12, and the second secondary fluid path 18B connects the sample inlet 14 and the secondary reaction chamber 50. A second primary recess 18C in the second surface 42 forms, together with the second primary foil 48, a part of the second primary fluid path 18A. A second secondary recess 18D in the second surface 42 forms, together with the second primary foil 48, a part of the second secondary fluid path 18B.
A fourth recess 29B in the second surface 42 forms, together with the second primary foil 48, a part of the fourth fluid path 29. The fourth fluid path 29 connects the outlet of the second chamber 28A at second valve 28B and the first fluid path 16.
A third primary recess 24B in the second surface 42 forms, together with the second primary foil 48, a part of the third primary fluid path 24.
A third secondary recess 56B in the second surface 42 forms, together with the second primary foil 48, a part of the third secondary fluid path 56.
A first strip chamber recess 64A forms a part of first flow strip chamber for
accommodating a first lateral flow strip. A second strip chamber recess 66A forms a part of second flow strip chamber 66 for accommodating a second lateral flow strip. The second primary foil 48 forms the bottom of the flow strip chambers 64, 66. A first end of the first lateral flow strip is arranged to overlap with the primary test chamber body part 22A such that test liquid in the primary test chamber 22 is fed to the first lateral flow strip. A first end of the second lateral flow strip is arranged to overlap with the secondary test chamber body part 54A such that test liquid in the secondary test chamber 54 is fed to the second lateral flow strip.
First holding elements 72, 74 are provided in the first flow strip chamber 64 of the body 4A. The first primary holding element 72 and the first secondary holding element 74 are configured to hold or fixate the first lateral flow strip in position between the body 4A and the second primary foil 48. Second holding elements 76, 78 are provided in the second flow strip chamber 66 of the body 4A. The second primary holding element 76 and the second secondary holding element 78 are configured to hold or fixate the second lateral flow strip in position between the body 4A and the second primary foil 48.
Fig. 8 shows a second or bottom view of the body 4A. The first fluid path 16 comprises and is split into a first branch formed by first branch recess 17A and second primary foil 48 and a second branch formed by second branch recess 17B and second primary foil 48. The first branch of the first fluid path feeds first buffer into a first inlet of the sample chamber formed by sample inlet and sample plug. The second branch of the second fluid path feeds first buffer into a second inlet of the sample chamber formed by sample inlet and sample plug. A plurality of sample chamber inlets in the microfluidic test device provides improved flushing of the sample. In one or more exemplary embodiments, the sample chamber only has a single inlet.
The second fluid path 18 comprises a first branch formed by first branch recess 19A and second primary foil 48 and a second branch formed by second branch recess 19B and second primary foil 48. Liquid from the sample chamber enters the first branch and the second branch of the second fluid path via respective first outlet and second outlet of the sample chamber. The first branch and the second branch of the second fluid path are joined in second fluid path joint 80 before splitting into second primary fluid path 18A and second secondary fluid path 18B.
Fig. 9 shows a cut out side view of the microfluidic test device 4A illustrating the heating assembly in further detail. The heating assembly 30 comprises a primary heating element 30A sandwiched between a first electrode layer 90 and a second electrode layer 92 for applying a primary voltage to the primary heating element. The heating assembly 30 (first electrode layer 90) is attached to the second primary foil 48 adjacent to and overlapping the primary and secondary reaction chambers 12, 50. A primary pellet of primary reaction material (not shown) is arranged in the primary reaction chamber, and a secondary pellet 94 of secondary reaction material is arranged in the secondary reaction chamber 50. The thin second primary foil 48 provides a good heat transport to reaction liquid in the reaction chambers 12, 50.
Thus, low heat loss from the heating assembly to the reaction chambers and precise control of the reaction liquid temperature is provided.
Fig. 10 shows an exemplary body 4B of a microfluidic test device. The sample chamber/sample inlet 14A has a single inlet from the first fluid path. Further, the sample chamber/sample inlet 14A has a single outlet to the second fluid path. In one or more exemplary microfluidic test devices, a single inlet from the first fluid path may be combined with two or more outlets to the second fluid path. Further, two or more inlets from the first fluid path may be combined with a single outlet to the second fluid path.
The use of the terms "first", "second", "third", "fourth", "primary", "secondary", etc. does not imply any particular order, but are included to identify individual elements. Moreover, the use of the terms "first", "second", "third", "fourth", "primary",
"secondary", etc. does not denote any order or importance, but rather these terms are used to distinguish one element from another. Note that the words "first", "second", "third", "fourth", "primary", and "secondary", are used here and elsewhere for labelling purposes only and are not intended to denote any specific spatial or temporal ordering. Furthermore, the labelling of a first element does not imply the presence of a second element and vice versa.
Although features have been shown and described, it will be understood that they are not intended to limit the claimed invention, and it will be made obvious to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the claimed invention. The specification and drawings are, accordingly to be regarded in an illustrative rather than restrictive sense. The claimed invention is intended to cover all alternatives, modifications, and equivalents.
LIST OF REFERENCES
2, 2A, 2B microfluidic test device
4, 4A, 4B body
6 first chamber
8 outlet
10 first valve
10A first valve body part
12 primary reaction chamber
12A primary reaction chamber plug
12B primary reaction chamber body part
14 sample inlet
16 first fluid path
16A first through-going bore
16B first recess
17A first branch recess of first fluid path
17B second branch recess of first fluid path
18 second fluid path
18A second primary fluid path
18B second secondary fluid path
18C second primary recess
18D second secondary recess
19A first branch recess of second fluid path
19B second branch recess of second fluid path
20 primary test part
22 primary test chamber
22A primary test chamber body part
24 third primary fluid path
24A primary through-going bore 24B third primary recess
26 primary valve
26A primary valve body part
28 flow driving device
28A second chamber
28B second valve
28C second valve body part
29 fourth fluid path
29A fourth through-going bore
29B fourth recess
30 heating assembly
30A primary heating element
32 first lateral flow strip
34 first end of first lateral flow strip
36 first end of body
38 second end of body
40 first surface of body
40A first primary surface of body
40B first secondary surface of body
42 second surface of body
44 first primary foil
46 first secondary foil
47 first tertiary foil
48 second primary foil
50 secondary reaction chamber
50A secondary reaction chamber plug
50B secondary reaction chamber body part
52 secondary test part 54 secondary test chamber
54A secondary test chamber body part
56 third secondary fluid path
56A secondary through-going bore
56B third secondary recess
58 secondary valve
58A secondary valve body part
60 second lateral flow strip
62 first end of second lateral flow strip
63 sample plug
64 first flow strip chamber
64A first strip chamber recess
66 second flow strip chamber
66A second strip chamber recess
68 first opening
70 second opening
72 first primary holding element
74 first secondary holding element
72 first primary holding element
74 first secondary holding element
76 second primary holding element
78 second secondary holding element
80 second fluid path joint
90 first electrode
92 second electrode
94 secondary pellet of secondary reaction material

Claims

1. Microfluidic test device comprising :
- a body;
- a first chamber having an outlet provided with a first valve and holding a first buffer having a first buffer volume;
- a primary reaction chamber;
- a sample inlet for receiving a sample and being configured for feeding a sample having a sample volume, into the medical test device;
- a first fluid path connecting the outlet of the first chamber and the sample inlet;
- a second fluid path connecting the sample inlet and the primary reaction chamber;
- a primary test part comprising a primary test chamber;
- a third primary fluid path connecting the primary reaction chamber and the primary test part;
- a primary valve arranged in the third primary fluid path;
- a flow driving device configured to move fluid from the primary reaction chamber to the primary test part; and
- a heating assembly configured to heat a reaction fluid in the primary reaction chamber.
2. Microfluidic test device according to claim 1, wherein the heating assembly is configured to heat the reaction fluid in the primary reaction chamber to a primary reaction temperature in the range from 30°C to 70°C.
3. Microfluidic test device according to claim 2, wherein the primary reaction temperature is in the range from 55°C to 65°C.
4. Microfluidic test device according to any of claims 1-3, wherein the heating assembly comprises a primary heating element adjacent the primary reaction chamber.
5. Microfluidic test device according to claim 4, wherein the primary heating element is configured to self-regulate to a primary temperature upon application of a primary voltage.
6. Microfluidic test device according to any of claims 4-5, wherein the primary heating element is connected to a first terminal and a second terminal for applying a voltage to the primary heating element.
7. Microfluidic test device according to any of claims 4-6, wherein the primary heating element comprises a resin material and/or one or more polymers.
8. Microfluidic test device according to any of claims 1-7, wherein the microfluidic test device comprises:
- a secondary test part comprising a secondary test chamber;
- a third secondary fluid path connecting the primary reaction chamber and the secondary test part; and
- a secondary valve arranged in the third secondary fluid path,
wherein the flow driving device is configured to move fluid from the primary reaction chamber to the secondary test part.
9. Microfluidic test device according to any of claims 1-7, wherein the microfluidic test device comprises:
- a secondary reaction chamber, wherein the second fluid path connects the sample inlet and the secondary reaction chamber;
- a secondary test part comprising a secondary test chamber;
- a third secondary fluid path connecting the secondary reaction chamber and the secondary test part; and - a secondary valve arranged in the third secondary fluid path, wherein the flow driving device is configured to move fluid from the secondary reaction chamber to the secondary test part.
10. Microfluidic test device according to claim 9, wherein the heating assembly is configured to heat a reaction fluid in the secondary reaction chamber to a secondary reaction temperature in the range from 30°C to 70°C.
11. Microfluidic test device according to any of claims 1-10, wherein the flow driving device comprises a second chamber having an outlet provided with a second valve, wherein the outlet of the second chamber is connected to the first fluid path or the second fluid path.
12. Microfluidic test device according to any of claims 1-11, wherein the primary valve is configured to open when the pressure on the inlet side of the primary valve is larger than a primary pressure threshold.
13. Microfluidic test device according to any of claims 1-12, wherein the microfluidic test system comprises a seal covering the sample inlet.
14. Microfluidic test device according to any of claims 1-13, wherein the primary test part comprises a first lateral flow strip having a first end connected to an outlet of the primary test chamber.
15. Microfluidic device according to claim 14, wherein the microfluidic test device comprises a primary gas spring chamber.
PCT/EP2018/054330 2017-02-22 2018-02-22 Microfluidic test device WO2018153950A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021073582A1 (en) * 2019-10-18 2021-04-22 利多(香港)有限公司 Microfluidic chip for analyte detection

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997027324A1 (en) * 1996-01-24 1997-07-31 Sarnoff Corporation Parallel reaction cassette and associated devices
US20020022261A1 (en) * 1995-06-29 2002-02-21 Anderson Rolfe C. Miniaturized genetic analysis systems and methods
US6663833B1 (en) * 1998-03-10 2003-12-16 Strategic Diagnostics Inc. Integrated assay device and methods of production and use
US20160175835A1 (en) * 2013-07-29 2016-06-23 Atlas Genetics Limited Fluidic cartridge and method for processing a liquid sample
US20160310948A1 (en) * 2015-04-24 2016-10-27 Mesa Biotech, Inc. Fluidic Test Cassette

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020022261A1 (en) * 1995-06-29 2002-02-21 Anderson Rolfe C. Miniaturized genetic analysis systems and methods
WO1997027324A1 (en) * 1996-01-24 1997-07-31 Sarnoff Corporation Parallel reaction cassette and associated devices
US6663833B1 (en) * 1998-03-10 2003-12-16 Strategic Diagnostics Inc. Integrated assay device and methods of production and use
US20160175835A1 (en) * 2013-07-29 2016-06-23 Atlas Genetics Limited Fluidic cartridge and method for processing a liquid sample
US20160310948A1 (en) * 2015-04-24 2016-10-27 Mesa Biotech, Inc. Fluidic Test Cassette

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021073582A1 (en) * 2019-10-18 2021-04-22 利多(香港)有限公司 Microfluidic chip for analyte detection

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