Particle isolation/enrichment using continuous closed-loop micro-fluidics

Patent metadata

Field	Value
Publication number	US-10697871-B2
Application number	US-201715726746-A
Country	US
Kind code	B2
Filing date	Oct 6, 2017
Priority date	Oct 7, 2016
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

The present invention encompasses a micro-fluidic system having a closed-loop configuration in which inertial micro-fluidic separation of particles and/or cells is continuously repeated by feeding part of the output back to the input so that the purity and/or concentration of the particles and/or cell is maximized. The invention also includes methods of using the micro-fluidic system.

First claim

What is claimed is:

1. A micro-fluidic system comprising:
a. At least one inlet reservoir;
b. At least one output reservoir;
c. A first spiral microchannel comprising a first inlet in fluid communication with an inlet reservoir, a first outlet in fluid communication with the inlet reservoir, and a second outlet in fluid communication with an output reservoir; wherein said first spiral microchannel is configured to separate particles from a sample fluid comprising a mixture of particles, wherein the first spiral microchannel has a trapezoidal cross section defined by a radially inner side, a radially outer side, a bottom side, and a top side, the cross section having i) the radially inner side and the radially outer side unequal in height, or ii) the radially inner side equal in height to the radially outer side, and wherein the top side has at least two continuous straight sections, each unequal in width to the bottom side;
wherein the micro-fluidic system is configured to provide a closed loop recirculation of the sample fluid through the first spiral microchannel.

2. The micro-fluidic system of claim 1 , wherein the spiral microchannel comprises at least 2 loops.

3. The micro-fluidic system of 1 , claim wherein the first spiral microchannel further comprises a second inlet in fluid communication with a second inlet reservoir.

4. The micro-fluidic system of claim 1 , wherein the first spiral microchannel cross section has (a) the height of the radially inner side larger than the height of the radially outer side, or (b) the height of the radially inner side is smaller than the height of the radially outer side, or (c) the top side includes at least one step forming a stepped profile, or (d) the top side includes at least one shallow region in between the radially inner side and the radially outer side.

5. The micro-fluidic system of claim 1 , wherein the first spiral microchannel has a right trapezoidal cross section.

6. The micro-fluidic system of claim 1 , wherein the top side of the first spiral microchannel cross section is curved.

7. The micro-fluidic system of claim 1 , wherein the bottom side of the first spiral microchannel cross section is curved.

8. The micro-fluidic system of claim 1 , wherein the radially inner side of the first spiral microchannel cross section has a height between about 20 microns and about 200 microns, and wherein the radially outer side of the first spiral microchannel cross section has a height between about 20 microns and about 200 microns.

9. The micro-fluidic system of claim 1 , wherein the bottom side of the first spiral microchannel cross section has a width between about 100 microns and about 2000 microns, and wherein the top side of the first spiral microchannel cross section has a width between about 100 microns and about 2000 microns.

10. The micro-fluidic system of claim 1 , wherein the first spiral microchannel has a radius of curvature between about 2.5 mm and about 25 mm.

11. The micro-fluidic system of claim 1 , wherein the first spiral microchannel has a length between about 4 cm and about 100 cm.

12. The micro-fluidic system of claim 1 , further comprising a second spiral microchannel disposed between (a) the first outlet of said first spiral microchannel and the inlet reservoir and in fluid communication therewith, (b) the second outlet of said first spiral microchannel and the output reservoir and in fluid communication therewith, or (c) the output reservoir and the inlet reservoir and in fluid communication therewith.

13. The micro-fluidic system of claim 12 , wherein the second spiral microchannel is disposed between the output reservoir and the inlet reservoir and in fluid communication therewith.

14. The micro-fluidic system of claim 12 , wherein the second spiral microchannel has a non-rectangular cross section.

15. The micro-fluidic system of claim 14 , wherein the second spiral microchannel has a trapezoidal cross section defined by a radially inner side, a radially outer side, a bottom side, and a top side, the cross section having a) the radially inner side and the radially outer side unequal in height, or b) the radially inner side equal in height to the radially outer side, and wherein the top side has at least two continuous straight sections, each unequal in width to the bottom side.

16. The micro-fluidic system of claim 15 , wherein the second spiral microchannel cross section has (a) the height of the radially inner side larger than the height of the radially outer side, or (b) the height of the radially inner side is smaller than the height of the radially outer side, or (c) the top side includes at least one step forming a stepped profile, or (d) the top side includes at least one shallow region in between the radially inner side and the radially outer side.

17. The micro-fluidic system of claim 14 , wherein the second spiral microchannel has a right trapezoidal cross section.

18. The micro-fluidic system of claim 1 , wherein the first inlet of the first spiral microchannel is the only inlet of the first spiral microchannel.

19. The micro-fluidic system of claim 1 , wherein the first spiral microchannel comprises a second inlet, wherein the second inlet is in fluid communication with a reservoir other than the inlet reservoir.

20. The micro-fluidic system of claim 1 , wherein the first spiral microchannel further comprises a second inlet, wherein the second inlet is in fluid communication with the output reservoir.

21. The method of claim 20 , wherein the output reservoir comprises a second background fluid, wherein the second background fluid is different from that of the sample fluid.

22. The micro-fluidic system of claim 1 , wherein the first inlet is the only inlet of the first spiral microchannel and the first inlet is on the interior of the spiral microchannel.

23. The micro-fluidic system of claim 1 , wherein the first and second outlets are on the circumference of the spiral microchannel.

24. The micro-fluidic system of claim 1 , wherein the first inlet is the only inlet of the first spiral microchannel and the first inlet is on the circumference of the spiral microchannel.

25. The micro-fluidic system of claim 1 , wherein the first and second outlets are on the interior of the spiral microchannel.

26. The micro-fluidic system of claim 1 , wherein at least one of the first and second outlets is located on the radially inner side of the first spiral microchannel.

27. The micro-fluidic system of claim 1 , wherein at least one of the first and second outlets is located on the radially outer side of the first spiral microchannel.

28. The micro-fluidic system of claim 1 , further comprising a pump configured to pump fluid from the inlet reservoir to the first inlet of the first spiral microchannel.

29. The micro-fluidic system of claim 1 , wherein the first spiral microchannel is located on a support thereby creating a first layer and wherein a plurality of such layers is stacked.

30. A method of separating particles from a sample fluid comprising a mixture of particles comprising the steps of:
a. introducing the sample fluid into the inlet reservoir of the micro-fluidic system according to claim 1 ,
b. directing the sample fluid from the inlet reservoir into the first inlet of the first spiral microchannel, bifurcating the fluid into a first stream cont

Assignees

• Massachusetts Inst Technology

Inventors

• Ryu Hyunryul
• Choi Kyungyong
• Han Jongyoon

Classifications

• B01L3/502776

  specially adapted for focusing or laminating flows · CPC title

• B01L2300/088

  Channel loops · CPC title

• G01N2015/1006

  for cytology · CPC title

• B01L2300/0883

  Serpentine channels · CPC title

• G01N2001/4088

  filtration · CPC title