Microfluidic device, use and methods

• US 10,220,389 B2
• Filed: 09/30/2014
• Issued: 03/05/2019
• Est. Priority Date: 09/30/2013
• Status: Active Grant

• Current Assignee: Capitainer Ab
• Original Assignee: Capitainer Ab
• Inventors: Stemme, Goran, Lenk, Gabriel, Beck, Olof, Roxhed, Niclas
• Primary Examiner(s): Hyun, Paul S
• Application Number:
  US15/025,524
• Publication Number:
  US 20160279634A1
• Time in Patent Office: 1,617 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/126 Paper
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: F16K 2099/0084 Chemistry or biology, e.g. "lab-on-a-chip" technology
• CPC Class Codes: F16K 2099/0086 Medical applications
• CPC Class Codes: F16K 99/003 Valves for single use only
• CPC Class Codes: F16K 99/0057 the fluid being the circulating fluid itself, e.g. check valves

Abstract

A microfluidic device comprises an inlet port for liquid, and a capillary channel in fluid connection to the inlet port for receiving liquid from the inlet port, the channel having a defined volume. At least one dissolvable valve is provided comprising a dissolvable membrane having a first side oriented towards the capillary channel, and a capillary 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. A method of controlling a flow of liquid uses such a microfluidic device.

Claims

1. A metering microfluidic device comprising

an inlet port for delivering a volume of liquid,

a metering capillary channel in fluid connection to the inlet port for receiving liquid from the inlet port, the metering capillary channel having an inlet portion, an outlet portion and a defined volume, and

at least one first dissolvable valve comprising a first dissolvable membrane having a first side oriented towards the metering capillary channel, and a capillary means, wherein the capillary means is formed of a layer of porous absorbent material and connected to a second side of the first dissolvable membrane such that when the first dissolvable membrane is dissolved by the liquid, liquid is transported through the at least one first dissolvable valve to the second side of the first dissolvable membrane by capillary action,

wherein the at least one first dissolvable valve is in capillary connection to the outlet portion of the metering capillary channel and arranged for transporting a metered volume of liquid from the metering capillary channel to the capillary means when the first dissolvable membrane is dissolved,

wherein at least one layer of dissolvable material forms the first dissolvable membrane, and the layer of porous absorbent material contacts the at least one layer of dissolvable material, and

wherein a laminate of layers of material define a flow path for the liquid and comprises the at least one layer of dissolvable material forming the first dissolvable membrane and the layer of porous absorbent material forming the capillary means.

2. A metering microfluidic device according to claim 1, comprising

a second dissolvable membrane connected to the inlet port,

wherein the capillary means is adapted for removing liquid supplied to the inlet port which is in excess of the liquid delivered to the metering capillary channel when the second dissolvable membrane is dissolved by liquid and for removing liquid from the outlet portion when the first dissolvable membrane is dissolved by liquid, and

wherein the first and second dissolvable membranes and the metering capillary channel are configured such that the second membrane is dissolved by the excess liquid before the first membrane is dissolved.

3. The microfluidic device according to claim 1, wherein the inlet port comprises an inlet chamber for receiving liquid and wherein a second dissolvable valve comprising a second dissolvable membrane is connected to the inlet chamber for transporting excess liquid from the inlet chamber to the capillary means when the second dissolvable membrane of the second dissolvable valve is dissolved.

4. The microfluidic device according to claim 1, wherein the metering capillary channel comprises a main capillary channel and a plurality of capillary side channels arranged along the main capillary channel and the capillary side channels are connected to a respective plurality of side channel dissolvable valves, respectively comprising dissolvable membranes, wherein the capillary means is connected to the respective plurality of side channel dissolvable valves to collect liquid from the plurality of side channel dissolvable valves.

5. The microfluidic device according to claim 1, wherein the device further comprises a plurality of dissolvable valves, distributed along a capillary flow path comprising the metering capillary channel.

6. The microfluidic device according to claim 5, wherein the metering capillary channel comprises a branched capillary channel structure comprising a plurality of capillary side arms connected to the plurality of dissolvable valves.

7. The microfluidic device according to claim 1, wherein the first side of the first dissolvable membrane of the dissolvable valve is also connected to a capillary dead end channel, configured such that liquid dissolving the first dissolvable membrane is transported into the capillary dead end channel by capillary forces.

8. The microfluidic device according to claim 7, further comprising a plurality of dissolvable valves arranged in series along the metering capillary channel and connected to a respective plurality of capillary dead end channels.

9. The microfluidic device according claim 1, wherein the first dissolvable membrane comprises at least one reagent or particle to be released into the liquid.

10. The microfluidic device according to claim 1, comprising a plasma separation membrane for separating plasma from whole blood.

11. The microfluidic device according to claim 1, wherein the laminate comprises a first layer of material forming the metering capillary channel.

12. The microfluidic device according to claim 1, wherein the porous absorbent material is an absorbent paper matrix.

13. A method of providing a metered volume of liquid sample in a microfluidic device according to claim 1, comprising

(i) introducing a liquid sample with an undefined volume to the inlet port,

(ii) metering a defined volume of the liquid sample by filling the metering capillary channel, wherein the defined volume is less than the undefined volume,

(iii) removing liquid which is in excess of the defined volume from the inlet port,

(iv) dissolving the at least one first dissolvable valve comprising the first dissolvable membrane, and

(v) transporting the metered liquid through the at least one first dissolvable valve to the second side of the first dissolvable membrane by means of capillary action in the capillary means.

14. The method according to claim 13, wherein the porous absorbent material is an absorbent paper matrix.

15. The method according to claim 13 wherein the inlet port comprises an inlet chamber, wherein the excess liquid is removed from the inlet port by providing at least one dissolvable membrane in connection to the inlet port, said inlet port dissolvable membrane comprising material dissolvable by the liquid, having a first side oriented towards the inlet chamber, and an inlet capillary means connected to a second side of the inlet port dissolvable membrane, the method comprising

dissolving the inlet port dissolvable membrane by the excess liquid, and

transporting the excess liquid to the second side of the inlet port dissolvable membrane by means of capillary action in the inlet capillary means.

16. A metering microfluidic device, comprising

an inlet port for delivering a volume of liquid,

a metering capillary channel in fluid connection to the inlet port for receiving liquid from the inlet port, the metering capillary channel having an inlet portion, an outlet portion and a defined volume, and

at least one dissolvable valve comprising a dissolvable membrane having a first side oriented towards the metering capillary channel, and a capillary means connected to a second side of the dissolvable membrane such that when the dissolvable membrane is dissolved by the liquid, liquid is transported through the at least one dissolvable valve to the second side of the dissolvable membrane by capillary action,

wherein the at least one dissolvable valve is in capillary connection to the outlet portion of the metering capillary channel and arranged for transporting a metered volume of liquid from the metering capillary channel to the capillary means when the dissolvable membrane is dissolved,

wherein a laminate of layers of material define a flow path for the liquid and comprises at least one layer of dissolvable material forming the dissolvable membrane, and

wherein the device comprises a plurality of dissolvable membranes formed by one and the same layer of dissolvable material in the microfluidic device.

17. The microfluidic device according to claim 16, wherein the flow path further comprises additional capillary channels on both sides of the layer of dissolvable material, wherein a plurality of dissolvable valves comprising the plurality of dissolvable membranes are formed at flow path crossings across the layer of dissolvable material.