Microfluidic cartridge

• US 8,105,783 B2
• Filed: 09/26/2008
• Issued: 01/31/2012
• Est. Priority Date: 07/13/2007
• Status: Active Grant

• Current Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Original Assignee: HandyLab Incorporated (Becton, Dickinson & Co)
• Inventors: Handique, Kalyan
• Primary Examiner(s): Kim, Young J
• Application Number:
  US12/239,537
• Publication Number:
  US 20090130719A1
• Time in Patent Office: 1,222 Days
• Field of Search: None
• US Class Current: 435/6.12
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0809 rectangular shaped
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2300/1844 using fans
• CPC Class Codes: B01L 2300/1894 Cooling means; Cryo cooling
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 : 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006

Abstract

The technology described herein generally relates to microfluidic cartridges configured to amplify and detect polynucleotides extracted from multiple biological samples in parallel. The technology includes a microfluidic substrate, comprising: a plurality of sample lanes, wherein each of the plurality of sample lanes comprises a microfluidic network having, in fluid communication with one another: an inlet; a first valve and a second valve; a first channel leading from the inlet, via the first valve, to a reaction chamber; and a second channel leading from the reaction chamber, via the second valve, to a vent.

Claims

1. A microfluidic substrate, comprising:

a plurality of sample lanes, wherein each of the plurality of sample lanes comprises a microfluidic network having, in fluid communication with one another;

an inlet;

a first valve and a second valve;

a reaction chamber;

a vent;

a first channel leading from the inlet, via the first valve, to the reaction chamber; and

a second channel leading from the reaction chamber, via the second valve, to the vent;

wherein the first and second valves are co-planar with the first and second channels in the microfluidic network and wherein the first and second valves each comprise a temperature responsive substance that melts upon heating and seals the first and second channels.

2. The microfluidic substrate of claim 1, wherein each of the plurality of sample lanes is configured to amplify one or more polynucleotides independently of the other lanes.

3. The microfluidic substrate of claim 1, configured to carry out real-time PCR in at least one of the reaction chambers.

4. The microfluidic substrate of claim 1, wherein each of the inlets is configured to accept a quantity of sample from a pipette tip.

5. The microfluidic substrate of claim 4, wherein the quantity of sample is from 1-20 μ

l.

6. The microfluidic substrate of claim 4, wherein an inlet comprises an inverted frustoconical structure of at least 1 mm height, and having a diameter at its widest point that accepts entry of a pipette tip, of from 1-5 mm.

7. The microfluidic substrate of claim 1, wherein the inlets of the respective plurality of sample lanes are spaced apart from one another to permit simultaneous loading from a multiple-pipette head dispenser.

8. The microfluidic substrate of claim 1, wherein the reaction chamber has a volume of 3-5 μ

l.

9. The microfluidic substrate of claim 1, wherein the plurality of sample lanes is 12 lanes.

10. The microfluidic substrate of claim 1, further comprising a fluorescence detection window situated over each of the reaction chambers.

11. A microfluidic cartridge comprising the microfluidic substrate of claim 1.

12. The microfluidic cartridge of claim 11, further comprising a registration member that ensures that the cartridge is received by a complementary diagnostic apparatus in a single orientation.

13. The microfluidic cartridge of claim 11, wherein each of the microfluidic networks, including the reaction chambers, the inlet holes and the valves for isolating the reaction chambers, is defined in a single substrate.

14. The microfluidic cartridge of claim 11, wherein the substrate is a rigid substrate and impervious to air or liquid, and entry or exit of air or liquid during operation of the cartridge is only possible through the inlet or a vent.

15. A microfluidic cartridge, comprising:

a substrate having an upper side and an opposed lower side, wherein the substrate comprises a plurality of sample lanes, wherein each lane of the plurality of sample lanes comprises a microfluidic network having, in fluid communication with one another;

an inlet;

a first valve and a second valve;

a first channel leading from the inlet, via the first valve, to a reaction chamber;

a second channel leading from the reaction chamber, via the second valve, to a vent; and

a label, attached to the upper side, wherein each valve has a wax loading hole extending to the upper side of the substrate, and wherein the label covers and seals the loading holes.

16. The cartridge of claim 15, wherein the microfluidic network is configured so that the time required to fill from the inlet to the second valve is less than 50% of the time required to fill up to the exit vent.

17. The cartridge of claim 15, wherein each microfluidic network comprises an overflow reservoir to contain extra liquid dispensed into the cartridge.

18. The cartridge of claim 15, wherein a 2-D barcode sample identifier is present on the label.

19. The cartridge of claim 15, further comprising two or more positioning elements for use when filling the valves with thermally responsive material.

20. The cartridge of claim 15, configured to be stackable.

21. The cartridge of claim 15, wherein the substrate comprises two ridges, one of each situated along each of two opposite edges of the cartridge, the ridges disposed on the upper side of the substrate.

22. The cartridge of claim 21, wherein the two ridges are configured to permit the cartridge to be supported horizontally on a tray, but keeping the lower side of the substrate below the tray.

23. A microfluidic substrate, comprising:

a plurality of sample lanes, wherein each of the plurality of sample lanes comprises a microfluidic network having, in fluid communication with one another;

an inlet;

a first valve and a second valve;

a reaction chamber;

a vent;

a first channel leading from the inlet, via the first valve, to the reaction chamber; and

a second channel leading from the reaction chamber, via the second valve, to the vent;

wherein the first and second valves comprise a temperature responsive substance that melts upon heating and seals the reaction chamber.

24. The microfluidic substrate of claim 23, wherein each of the plurality of sample lanes is configured to amplify one or more polynucleotides independently of the other lanes.

25. The microfluidic substrate of claim 23, configured to carry out real-time PCR in at least one of the reaction chambers.

26. The microfluidic substrate of claim 23, wherein each of the inlets is configured to seal with and accept a quantity of sample from a pipette tip.

27. The microfluidic substrate of claim 26, wherein the quantity of sample is from 1-20 μ

l.

28. The microfluidic substrate of claim 26, wherein an inlet comprises an inverted frustoconical structure of at least 1 mm height, and having a diameter at its widest point that accepts entry of a pipette tip, of from 1-5 mm.

29. The microfluidic substrate of claim 23, wherein the inlets of the respective plurality of sample lanes are spaced apart from one another to permit simultaneous loading from a multiple-pipette head dispenser.

30. The microfluidic substrate of claim 23, wherein the reaction chamber has a volume of 3-5 μ

l.

31. The microfluidic substrate of claim 23, wherein the plurality of sample lanes is 12 lanes.

32. The microfluidic substrate of claim 23, further comprising a fluorescence detection window situated over each of the reaction chambers.

33. A microfluidic cartridge comprising the microfluidic substrate of claim 23.

34. The microfluidic cartridge of claim 33, further comprising a registration structure that ensures that the cartridge is received by a complementary diagnostic apparatus in a single orientation.

35. The microfluidic cartridge of claim 33, wherein each of the microfluidic networks, including the PCR reaction chambers, the inlet holes and the valves for isolating the PCR reaction chambers, is defined in a single substrate.

36. The microfluidic cartridge of claim 33, wherein the substrate is a rigid substrate and impervious to air or liquid, and entry or exit of air or liquid during operation of the cartridge is substantially possible only through the inlet or a vent.