METHODS AND DEVICES FOR SAMPLE LYSIS

• US 20140087359A1
• Filed: 09/20/2013
• Published: 03/27/2014
• Est. Priority Date: 09/21/2012
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: NJOROGE, Samuel, GORMAN, John, MALTEZOS, George, SCHERER, Axel
• Granted Patent: US 9,580,679 B2
• Time in Patent Office: Days
• US Class Current: 435/2
• CPC Class Codes: B01L 2300/1883 using thermal insulation
• 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 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: C12M 21/00 Bioreactors or fermenters specially adapted for specific uses digesters for manure A01C3/023; apparatus for PCR B01L7/52; destroying or transforming solid waste B09B3/00; methods for genetic engineering C12N15/00, C12Q1/68; nucleic acid amplification reactions C12Q1/6844
• CPC Class Codes: C12M 47/06 Hydrolysis; Cell lysis; Extraction of intracellular or cell wall material lysis of microorganisms C12N1/06; extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: C12N 1/06 Lysis of microorganisms
• CPC Class Codes: C12N 1/066 by physical methods
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027

Abstract

Disclosed herein are methods and systems for use in preparing a sample. The methods and systems may be used for lysing one or more structures in a sample (e.g., cells, viral particles, etc.). The methods and compositions may comprise a microfluidic chip or use thereof. The microfluidic chips disclosed herein may comprise (a) a substrate comprising a chamber, wherein at least one mechanical element may be located within the chamber; (b) a thermal element in contact with the chamber; and (c) at least one aperture within the surface of the substrate, wherein the aperture may be configured to insulate the chamber.

Claims

1. A microfluidic chip comprising:

a. a chamber, wherein at least one stir bar is located within the chamber;

b. a thermal device in thermal contact with the chamber; and

c. at least one insulative groove within the surface of the chip, which is configured to insulate the chamber.

3. The microfluidic chip of claim 1 or 2, wherein the thermal device is a heater.

4. The microfluidic chip of claim 1 or 2, wherein the thermal device is a cooler.

5. The microfluidic chip of claim 1 or 2, wherein the at least one insulative groove is nine insulative grooves.

6. The microfluidic chip of claim 1 or 2, wherein the at least one insulative groove is a plurality of grooves positioned around the chamber.

7. The microfluidic chip of claim 1 or 2, wherein the at least one insulative groove is filled with an insulative material.

8. The microfluidic chip of claim 1, wherein the stir bar is composed of magnetic material.

9. The microfluidic chip of claim 1 or 2, wherein the microfluidic chip is coupled to an external magnetic field.

13. The microfluidic chip of claim 1 or 2, further comprising a vent.

14. The microfluidic chip of claim 1 or 2, further comprising a filter.

15. The microfluidic chip of claim 1 or 2, further comprising one or more additional chambers.

16. The microfluidic chip of claim 1 or 2, further comprising a thermal conductor.

17. The microfluidic chip of claim 1 or 2, further comprising a thermal transducer.

18. The microfluidic chip of claim 1 or 2, further comprising a thermal sensor.

19. The microfluidic chip of claim 1 or 2, further comprising a pouch.

20. The microfluidic chip of claim 19, wherein the pouch is made of polypropylene, polyethylene, polyethylene terephthalate (PET) or combinations thereof.

21. The microfluidic chip of claim 1 or 2, wherein the microfluidic chip is manufactured by using converted-tape technology.

2. A microfluidic chip comprising:

a. a chamber, wherein a plurality of granular particles is located within the chamber;

b. a thermal device in thermal contact with the chamber; and

c. at least one insulative groove within the surface of the chip, which is configured to insulate the chamber.

10. The microfluidic chip of claim 2, wherein the granular particles are beads.

11. The microfluidic chip of claim 10, wherein the beads are made of glass or cubic-zirconium.

12. The microfluidic chip of claim 10, wherein the beads are magnetic beads.

22. A microfluidic chip comprising:

a. a first chamber; and

b. a herringbone mixer in fluidic contact with the first chamber, wherein the herringbone mixer is in thermal contact with at least one thermal device.

23. The microfluidic chip of claim 22, wherein the herringbone mixer is a staggered herringbone mixer.

24. The microfluidic chip of claim 22, wherein the thermal device is a resistive heater.

25. A microfluidic chip comprising:

a. a first chamber;

b. a first herringbone mixer in fluidic contact with the first chamber;

c. a second chamber fluidly connected to the first herringbone mixer; and

d. a second herringbone mixer fluidly connected to the second chamber;

wherein the second chamber is positioned between the first and second herringbone mixers.

26. The microfluidic chip of claim 25, further comprising a thermal device in thermal contact with the first herringbone mixer.

27. A method of lysing a sample comprising:

a. introducing a sample into a chamber within a microfluidic device; and

b. lysing the sample by heating the sample within the chamber, wherein the chamber is separated from a portion of the device by at least one insulative groove.

28. The method of claim 27, wherein the lysing of the sample also comprises chemical or mechanical lysis.

29. The method of claim 27, wherein the lysing the sample further comprises agitating the sample.

30. The method of claim 27, further comprising agitating the sample with a stir bar, wherein the stir bar is located within the chamber.

31. The method of claim 27, further comprising agitating the sample with a plurality of beads within the chamber.

32. The method of claim 27, further comprising agitating the sample with by applying pressure.

33. The method of claim 27, wherein lysing the sample further comprises mixing the sample with one or more reagents.

34. A method of lysing a sample comprising lysing a sample by flowing the sample through a herringbone mixer within a microfluidic chip, and providing thermal energy to the sample within the herringbone mixer.

35. The method of claim 34, wherein the herringbone mixer is in a serpentine shape.

36. The method of claim 34, further comprising flowing the sample through an additional herringbone mixer.

37. The method of claim 34, wherein the herringbone mixer contains one or more reagents.

38. The method of claim 34, wherein lysing the sample further comprises mixing the sample with one or more reagents.

39. The method of claim 34, wherein the sample contains blood or sputum.

40. A method of lysing a sample comprising:

a. introducing the sample into tubing, wherein the tubing is spirally wrapped around a heating or cooling cartridge and wherein the tubing comprises lysis reagents; and

b. applying negative and positive pressure cycles to the tubing in order to promote mixing of the sample with the lysis reagents.

41. The method of claim 40, wherein the thermal device comprises a heating cartridge.

42. The method of claim 40, wherein the negative and positive pressure is applied with a plunger or linear actuator in fluid connection with the tubing.

43. The method of claim 40, further comprising a thermal transducer.

44. The method of claim 43, wherein the thermal device is coupled to the thermal transducer.

45. The method of claim 40, wherein the sidewalls of the tubing contain lyophilized lysis reagents.

46. The method of claim 40, wherein the tubing comprises liquid lysis reagents.