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EP-4735175-A1 - TIMED VALVE

EP4735175A1EP 4735175 A1EP4735175 A1EP 4735175A1EP-4735175-A1

Abstract

The present invention relates to a microfluidic device comprising (i) a vent [104], which opens upon dissolution of an air-impermeable and water-soluble membrane [102] and (ii) means [105] for increasing hydraulic resistance to liquid flow located upstream of said vent [104]. The invention further relates to use of the device of the invention to partition a volume of liquid and to a method to partition a volume of liquid.

Inventors

  • LAMMERTYN, JEROEN
  • VLOEMANS, Dries
  • DAL DOSSO, Francesco

Assignees

  • Katholieke Universiteit Leuven

Dates

Publication Date
20260506
Application Date
20240628

Claims (13)

  1. 1. A microfluidic device comprising, a. an inlet [106] for liquid; b. a fluid conduit [101] in fluid connection with the inlet [106]; c. a first air-impermeable and water-soluble membrane [102] that (i) is closing a first opening [112] in a wall of the fluid conduit [101], (ii) is positioned to dissolve upon circulation of liquid through the fluid conduit [101], and (iii) has a first side oriented toward an inside of the fluid conduit [101]; d. a vent [104] that is in fluid connection with the other side of the first air-impermeable and water-soluble membrane [102] and wherein said vent [104] comprises means to prevent liquid flow through the first opening [112], while allowing circulation of air therethrough; e. means [105] for increasing hydraulic resistance to liquid flow, located downstream of the inlet [106] and upstream of the first opening [112]; f. an outlet [119], located downstream of the opening [112], and in fluid connection therewith.
  2. 2. The microfluidic device according to claim 1, wherein said means [105] for increasing hydraulic resistance to liquid flow comprise, a geometric flow resistance, a porous filtration element, a thermal expansion valve, a hydrogel swelling valve, a hydrophobic flow resistance, a plunger valve, a rotating valve, a pressure valve or a combination thereof.
  3. 3. The microfluidic device according to claim 1 or 2, wherein said means [105] for increasing hydraulic resistance to liquid flow comprise, a geometric flow resistance, a porous filtration element, a thermal expansion valve, a hydrogel swelling valve, a hydrophobic flow resistance, or a combination thereof.
  4. 4. The microfluidic device according to any one of claims 1 to 3, wherein said means [105] for increasing hydraulic resistance to liquid flow, comprise a filter.
  5. 5. The microfluidic device according to claim 4, wherein said filter is a plasma separation membrane [107],
  6. 6. The microfluidic device according to any one of claims 1 to 5, wherein said means [105] for increasing hydraulic resistance to liquid flow, comprise a single, or an array of, hollow microneedle(s) [111].
  7. 7. The microfluidic device according to any one of claims 1 to 6, wherein said means to prevent liquid flow through the first opening [112], while allowing circulation of air therethrough, comprise, or consist of, hydrophobic porous material [103],
  8. 8. The microfluidic device according to any one of claims 1 to 7, wherein said means [105] for increasing hydraulic resistance to liquid flow comprise: a. a first chamber [ 114] in fluid connection with the inlet [ 106] and with the fluid conduit [101]; b. a second air-impermeable and water-soluble membrane [118] that (i) is closing an opening [115] in a wall of the first chamber [114], (ii) is positioned to dissolve upon circulation of liquid through the first chamber [114], and (iii) has a first side oriented toward an inside of the first chamber [114]; c. a second chamber [116] that (i) is filled with a hydrophilic porous material [117], (ii) is in fluid connection with the other side of the second membrane [118] and (iii) comprises a trapped volume of gas in the pore of the hydrophilic porous material; and, d. a geometric restriction in the fluid connections upstream and downstream of the first chamber [114] .
  9. 9. The microfluidic device according to any one of claims 1 to 8, wherein said device further comprises a pump [108], downstream of, and in fluid connection with, the outlet [119],
  10. 10. The microfluidic device according to claim 9, wherein said pump [108] is a capillary pump.
  11. 11. Use of the microfluidic device according to any one of claims 1 to 10, to partition a volume of aqueous liquid.
  12. 12. A method to partition a volume of aqueous liquid comprising the steps of a. drawing in aqueous liquid through the fluid conduit [101] of the microfluidic device according to any one of claim 1 to 10; and, b. partitioning said aqueous liquid.
  13. 13. The method of claim 12, wherein step b does not require any user intervention to open and/or close valves nor the use of valves fitted with actuators.

Description

TIMED VALVE FIELD OF THE INVENTION The present invention relates to a microfluidic device comprising a vent, which opens upon dissolution of an air-impermeable and water-soluble membrane. The invention further relates to the use of the device of the invention for liquid partitioning. BACKGROUND OF THE INVENTION When displacing liquid within a microfluidic device, it is often necessary and desirable to isolate fluidically a subset of the liquid from a larger volume of liquid in a manner where the ability to displace the isolated liquid independently from the larger volume is retained without requiring an additional user intervention (e.g., transfer to another independent fluid container). This need is further illustrated by current practice in blood sampling. Currently, the blood collection step and the further manipulation and analysis of the sample are decoupled and require user intervention/actuation at several time points. Hereto, the sample first has to be collected from the patient after which it is transferred to the device (i.e., cartridge, cassette, paper strip) which is then used to perform further downstream liquid processes such as storage, sample preparation or (bio)chemical analysis. When the same device is used to both collect the sample (e.g., via microneedles) directly from a living organism (e.g., human body, animal or plant) and further process it downstream in the system, it is necessary to decouple the extracted sample liquid from the unlimited sample source (e.g., represented by the body bloodstream) in the living organism. Another relevant example is where it is desired to decouple the filtered and unfiltered liquid sample fractions (e.g., plasma and blood cell fractions during plasmapheresis) to avoid contamination. To achieve this decoupling, various types of microfluidic valving methods such as mechanical valves with moving elements, valving via heating and the like exist. However, most of these valves are very complex which make them too expensive for usage in disposable microfluidic systems and/or require user intervention to decouple fluidically the isolated volume of liquid from the larger liquid volume it is isolated from. US2016/279634 discloses a microfluidic device comprising an inlet and a capillary channel, i.e., fluid conduit, in connection therewith. A dissolvable valve is provided comprising a dissolvable membrane having a first side oriented towards the capillary channel, and capillary means connected to the second side of the dissolvable membrane such that when the membrane is dissolved by the liquid, liquid is transported through the valve to the second side of the membrane by capillary action. AU2014280043 discloses a microfluidic device comprising a sacrificial valve, e.g., water-soluble membrane, whose opening is triggered by the opening of a second valve, causing a retraction of a fluid spacer thus bringing liquid into contact with the dissolvable valve membrane. There is thus a need for a valving system that would allow to combine in a single step that does not require user actuation, the isolation of a smaller volume of liquid from a larger volume in a manner allowing further manipulation of the isolated liquid (e.g., by aspiration force). SUMMARY The present invention relates to a microfluidic device comprising, a. an inlet for liquid; b. a fluid conduit in fluid connection with the inlet; c. a first air-impermeable and water-soluble membrane that (i) is closing a first opening in a wall of the fluid conduit, (ii) is positioned to dissolve upon circulation of liquid through the fluid conduit, and (iii) has a first side oriented toward an inside of the fluid conduit; d. a vent that is in fluid connection with the other side of the first air-impermeable and water-soluble membrane and wherein said vent comprises means to prevent liquid flow through the first opening, while allowing circulation of air therethrough; e. means for increasing hydraulic resistance to liquid flow, located downstream of the inlet and upstream of the first opening; and, f. an outlet, located downstream of the opening, and in fluid connection therewith. In one embodiment, the device of the invention further comprises, a pump, downstream of, and in fluid connection with, the outlet.. In one embodiment, the microfluidic device comprises, a. an inlet for liquid; b. a fluid conduit in fluid connection with the inlet; c. a first air-impermeable and water-soluble membrane that (i) is closing a first opening in the wall of the fluid conduit, (ii) is positioned to dissolve upon circulation of liquid through the fluid conduit, and (iii) has a first side oriented toward the inside of the fluid conduit; d. a vent that is in fluid connection with the other side of the first air-impermeable and water-soluble membrane so that when the first membrane is opened by dissolution in liquid flowing through the fluid conduit, air can flow through the vent inside the fluid conduit and wherein said vent comp