IP Library Granted Patent US 10,782,223
Granted Patent B2
US 10,782,223 · App. 15/670,264 · Granted Sep 22, 2020

Label-free cellular manipulation and sorting via biocompatible ferrofluids

Inventor: Hur Koser (Branford, CT)
Assignee: YALE UNIVERSITY
G01N15/1056B01L3/50273B01L3/502715B01L3/502761B03C1/023B03C1/23B03C1/253B03C1/288B03C1/32C12M47/04C12N13/00B01L2200/0636B01L2200/0652B01L2300/06B01L2300/0848B03C2201/18B03C2201/24B03C2201/26G01N2015/0065G01N2015/1006G01N2015/1081
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,782,223
App. No.
15/670,264
Granted
Sep 22, 2020
Kind
B2
Abstract

A device for separating a sample of cells suspended in a bio-compatible ferrofluid is described. The device includes a microfluidic channel having a sample inlet, at least one output, and a length between the sample inlet and the at least one output, wherein a sample can be added to the sample inlet and flow along the length to the at least one outlet. The device includes a plurality of electrodes, wherein the microfluidic channel length transverses the plurality of electrodes, and further includes a power source for applying a current to the plurality of electrodes to create a magnetic field pattern along the length of the microfluidic channel. The present invention also includes a method for separating at least one cell type. The method includes the steps of suspending cells in a bio-compatible ferrofluid to form a sample, passing the sample through a microfluidic channel that transverses a plurality of electrodes, applying a current to the plurality of electrodes to create a magnetic field pattern along the length of the microfluidic channel, and sorting the cells into at least one output channel based on a variation of at least one of cell size, shape and elasticity.

Claims (54)

1. A device for separating a sample of particles suspended in a biocompatible ferrofluid, comprising:

a microfluidic channel having a sample inlet, at least one output, and a length between the sample inlet and the at least one output, wherein a sample can be added to the sample inlet and flow along the length to the at least one outlet;

a plurality of electrodes comprising a plurality of electrode layers, wherein the microfluidic channel length transverses at least a portion of the plurality of electrodes; and

a power source for applying a current to the plurality of electrodes to create a magnetic field pattern along the length of the microfluidic channel.

2. The device of claim 1 , wherein the spacing between electrodes is gradually increased.

3. The device of claim 1 , wherein the spacing between electrodes is gradually decreased.

4. The device of claim 1 , wherein the plurality of electrodes comprise at least one electrode layer.

5. The device of claim 1 , wherein the plurality of electrode layers is in a substantially orthogonal pattern.

6. The device of claim 1 , wherein the walls of the microfluidic channel length include a pocketed, a ridged, a grooved, a trenched or a sloped region.

7. The device of claim 1 , wherein the microfluidic channel length transverses at least a portion of the plurality of electrodes at an angle between about 1-90 degrees.

8. The device of claim 1 , wherein the particles are living cells.

9. A system for separating at least one target from a sample suspended in a biocompatible ferrofluid, comprising:

a microfluidic channel having a sample inlet, at least one output, and a length between the sample inlet and the at least one output, wherein a sample can be added to the sample inlet and flow along the length to the at least one outlet;

a plurality of electrodes, wherein the microfluidic channel length transverses at least a portion of the plurality of electrodes, and generating a magnetic field pattern along the length of the microfluidic channel when a current is applied to the electrodes; and

at least one target in a sample suspended in a biocompatible ferrofluid;

wherein the at least one target is separated from the remaining sample as the at least one target passes along at least a portion of the microfluidic channel length, and wherein the at least one target is a cell or a particle.

10. The system of claim 9 , wherein the sample comprises living cells.

11. The system of claim 10 , wherein the biocompatible ferrofluid comprises a suitable amount of ionic species to control the osmotic pressure on the cells to promote cell sustainability.

12. The system of claim 11 , wherein the biocompatible ferrofluid comprises a citrate concentration of between about 5-200 mM.

13. The system of claim 12 , wherein the biocompatible ferrofluid comprises a citrate concentration of about 40 mM.

14. The system of claim 10 , wherein the biocompatible ferrofluid has a pH of about 7.4.

15. The system of claim 9 , wherein the at least one target is separated based on target size.

16. The system of claim 9 , wherein the at least one target is separated based on target shape.

17. The system of claim 9 , wherein the at least one target is separated based on target elasticity.

18. The system of claim 9 , wherein the spacing between electrodes is gradually increased.

19. The system of claim 9 , wherein the spacing between electrodes is gradually decreased.

20. The system of claim 9 , wherein the target is separated by being directed to a selected outlet.

21. The system of claim 9 , wherein the target is trapped based on the spacing of electrodes.

22. The system of claim 9 , wherein the plurality of electrodes comprise at least one electrode layer.

23. The system of claim 9 , wherein the plurality of electrodes comprise a plurality of electrode layers.

24. The system of claim 23 , wherein the plurality of electrode layers is in a substantially orthogonal pattern.

25. The system of claim 9 , wherein the plurality of electrodes comprise a pattern of concentric circles.

26. The system of claim 9 , wherein the walls of the microfluidic channel length include a pocketed, a ridged, a grooved, a trenched or a sloped region.

27. The system of claim 9 , wherein the microfluidic channel length transverses at least a portion of the plurality of electrodes at an angle between about 1-90 degrees.

28. A method for separating at least one cell type, comprising:

suspending two or more cell types in a biocompatible ferrofluid to form a sample;

passing the sample through a microfluidic channel that transverses a plurality of electrodes;

applying a current to the plurality of electrodes to create a magnetic field pattern along the length of the microfluidic channel; and

sorting the cells into at least one output channel based on a variation of at least one of cell size, shape and elasticity;

wherein the cells are separated at an efficiency of at least about 90%.

29. The method of claim 28 , wherein the biocompatible ferrofluid comprises a suitable amount of ionic species to control the osmotic pressure on the cells to promote cell sustainability.

30. The method of claim 29 , wherein the biocompatible ferrofluid has a pH of about 7.4.

31. The method of claim 29 , wherein the biocompatible ferrofluid comprises a citrate concentration of between about 5-200 mM.

32. The method of claim 31 , wherein the biocompatible ferrofluid comprises a citrate concentration of about 40 mM.

33. The method of claim 28 , wherein the separated cells are being directed to a selected outlet.

34. The method of claim 28 , wherein the separated cells are being trapped based on the spacing of electrodes.

35. The method of claim 28 , wherein the size resolution in separating is less than about 10 μm.

36. The method of claim 28 , wherein the cells are separated in less than about 1 minute.

37. A system for separating at least one target from a sample suspended in a biocompatible ferrofluid, comprising:

a microfluidic channel having a sample inlet, at least one output, and a length between the sample inlet and the at least one output, wherein a sample can be added to the sample inlet and flow along the length to the at least one outlet;

a plurality of electrodes, wherein the microfluidic channel length transverses at least a portion of the plurality of electrodes, and generating a magnetic field pattern along the length of the microfluidic channel when a current is applied to the electrodes; and

at least one target in a sample suspended in a biocompatible ferrofluid;

wherein the at least one target is separated from the remaining sample as the at least one target passes along at least a portion of the microfluidic channel length, and

wherein the microfluidic channel length transverses at least a portion of the plurality of electrodes at an angle between about 1-90 degrees.

Continuity (6)
Continuation 15163890 · May 25, 2016
Continuation 14591492 · Jan 7, 2015
Continuation 13514331
Provisional Application 61267163 · Dec 7, 2009
Provisional Application 61407738 · Oct 28, 2010
Related Publication 20180128729A1 · May 10, 2018
Cited By (2)
US 12,678,800 US 12,704,509