Removing bubbles in a microfluidic device
Methods of removing bubbles from a microfluidic device are described where the flow is not stopped. Methods are described that combine pressure and flow to remove bubbles from a microfluidic device. Bubbles can be removed even where the device is made of a polymer that is largely gas impermeable.
1. A method of reducing bubble volume, comprising:
a) providing a microfluidic device comprising a microchannel, said microchannel comprises living cells attached thereto;
b) flowing fluid at a flow rate through said microchannel over said cells;
c) detecting a bubble, said bubble having a volume; and
d) reducing said bubble volume with pressure without stopping said flowing of said fluid.
2. The method of claim 1 , wherein said microchannel is in fluidic communication with a first reservoir at a first end of said microchannel, and a second reservoir at a second end of said microchannel.
3. The method of claim 1 , wherein said bubble of step c) is positioned against a polymer that is substantially gas impermeable.
4. The method of claim 2 , wherein said first reservoir comprises fluid under a first pressure and said second reservoir comprises fluid under a second pressure, wherein said first pressure is greater than said second pressure.
5. The method of claim 4 , wherein said first pressure is 21 kPa and said second pressure is 20 kPa.
6. The method of claim 1 , wherein said bubble is a gas bubble.
7. The method of claim 6 , wherein said gas is oxygen, nitrogen or a mixture thereof.
8. The method of claim 1 , wherein said bubble is an air bubble.
9. The method of claim 1 , wherein said flow rate is 40 uL/hr.
10. The method of claim 1 , wherein said fluid comprises culture media supplied to said living cells and said cells are still living after step d).
11. The method of claim 10 , wherein said media prior to step d) was degassed.
12. The method of claim 10 , wherein said media of step d) is unsaturated.
13. The method of claim 10 , wherein said media prior to step d) was not degassed.
14. The method of claim 1 , wherein step d) is performed for at least one 1 hour.
15. The method of claim 14 , wherein step d) is performed for 2 hours.
16. The method of claim 14 , further comprising e) introducing fluid into said microchannel, wherein said fluid has not been degassed.
17. A method of reducing bubble volume, comprising:
a) providing a microfluidic device comprising a microchannel, said microchannel comprises living cells attached thereto;
b) flowing fluid at a flow rate through said microchannel over said cells, wherein said fluid was treated prior to said flowing so as to render the fluid unsaturated;
c) detecting a bubble, said bubble having a volume; and
d) reducing said bubble volume with pressure over a period of time without stopping said flowing of said fluid, wherein living cells are in said microchannel after said period of time.
18. The method of claim 17 , wherein said microchannel is in fluidic communication with a first reservoir at a first end of said microchannel, and a second reservoir at a second end of said microchannel.
19. The method of claim 17 , wherein said bubble of step c) is positioned against a polymer that is substantially gas impermeable.
20. The method of claim 18 , wherein said first reservoir comprises fluid under a first pressure and said second reservoir comprises fluid under a second pressure, wherein said first pressure is greater than said second pressure.
21. The method of claim 20 , wherein the first pressure is greater by at least 0.5 kPa.
22. The method of claim 20 , wherein said first pressure is 21 kPa and said second pressure is 20 kPa.
23. The method of claim 17 , wherein said bubble is a gas bubble.
24. The method of claim 23 , wherein said gas is oxygen, nitrogen or a mixture thereof.
25. The method of claim 17 , wherein said bubble is an air bubble.
26. The method of claim 17 , wherein said flowing of fluid is at a flow rate of 40 uL/hr.