Method and apparatus for continuous removal of sub-micron sized particles in a closed loop liquid flow system

• US 10,675,641 B2
• Filed: 10/15/2018
• Issued: 06/09/2020
• Est. Priority Date: 08/25/2009
• Status: Active Grant

• Current Assignee: Nanoshell Company, LLC
• Original Assignee: Nanoshell Company, LLC
• Inventors: Ostafin, Agnes, Mizukami, Hiroshi
• Primary Examiner(s): Cleveland, Timothy C
• Application Number:
  US16/160,873
• Publication Number:
  US 20190151861A1
• Time in Patent Office: 603 Days
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3687 Chemical treatment A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3693 using separation based on different densities of components, e.g. centrifuging
• CPC Class Codes: A61M 1/3696 with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
• CPC Class Codes: B01D 21/262 by using a centrifuge
• CPC Class Codes: B01D 21/34 Controlling the feed distribution; Controlling the liquid level ; Control of process parameters
• CPC Class Codes: B04B 11/02 Continuous feeding or discharging; Control arrangements therefor
• CPC Class Codes: B04B 13/00 Control arrangements specially designed for centrifuges; Programme control of centrifuges control arrangements for feed, charge, or discharge B04B11/00
• CPC Class Codes: B04B 2005/045 having annular separation channels
• CPC Class Codes: B04B 2013/006 Interface detection or monitoring of separated components
• CPC Class Codes: B04B 5/0442 with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
• CPC Class Codes: B04B 7/08 Rotary bowls centrifugal casting machines B22D
• CPC Class Codes: C12M 33/10 by centrifugation centrifuges in general B04B; Cyclones cyclones in general B04C
• CPC Class Codes: C12M 47/04 Cell isolation or sorting purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04

Abstract

A centrifuge rotor having a curved shape is offset on a spinning rotor base and creates contiguous areas of low to high centrifugal force depending on the distances from the axis of the rotor base and a method of separating components in a fluid based upon a difference in density of the components, the method comprising the steps of providing to a rotor as described herein the fluid containing the mixed together components to be separated based upon the difference in density of the mixed together components; continuously flowing the components in the fluid to the rotor through an input tube connected to the input port while the rotor is spinning about a centrifugal axis of rotation; separating the components in the fluid into fractions based upon the difference in density of the mixed together components with the use of centrifugal force when the rotor is spinning; collecting components having i) a first density via a first tube connected to the output port at the first end on the rotor, ii) a second density via a second tube connected to the output port at the second end on the rotor, iii) a third density via a third tube connected to the output port at the junction on the rotor and iv) a fourth density via a fourth tube connected to the output port between the input port and the output port at the first end.

Claims

1. A rotor for a centrifuge used to separate a mixture of components in a fluid having different densities, the rotor comprising:

a hollow curved housing that has an inner wall and an outer wall, a top, a bottom and a first end and a second end wherein the inner wall is radially closer to an axis of rotation as compared to the outer wall;

the hollow curved housing being formed of a curved first rotor element that terminates at the first end of the curved housing and a curved second rotor element that terminates at the second end of the curved housing wherein the curved housing between the curved first rotor element and the curved second rotor element includes a junction that creates a change in an inner and outer radius of the first rotor element as compared to an inner and outer radius of the second rotor element;

an input port positioned on the inner wall of the first rotor element between an output port of the first end and an output port positioned on the inner wall of the junction;

an output port positioned on the inner wall of the first rotor element between the output port at the first end and the input port;

an output port in the second end; and

the hollow curved housing from the first end to the second end forming an about 150-360 degree curve about the axis of rotation;

wherein the first end is a distance d4 from the axis of rotation, the second end is a distance d3 from the axis of rotation and the junction is a distance dr from the axis of rotation with d4>

dr>

d3.

2. The rotor of claim 1 wherein the output port positioned on the inner wall of the junction is positioned at the center of the junction.

3. The rotor element of claim 1 wherein the hollow housing has a distance between an interior side of the inner wall and an interior side of the outer wall that is the same in the first rotor element and the second rotor element.

4. The rotor element of claim 1 wherein the curve is between 180-200 degrees.

5. The rotor element of claim 1 wherein the input port, the output port at the first end, and the output port at the second end are each positioned in the same horizontal plane of the rotor.

6. The rotor element of claim 1 wherein the input port is connectable to a tube.

7. The rotor element of claim 1 wherein the area defined by the first rotor element between d4 and dr is greater than the area defined by the second rotor element between dr and d3.

8. The rotor element of claim 1 wherein the output port at the first end, the output port at the second end, the output port near the junction and the output port between the output port at the first end and the output port near the junction are each connectable to a tube.

9. A method of separating components in a fluid based upon a difference in density of the components in the fluid when the components mixed together have at least four different densities, the method comprising the steps of:

providing to a rotor of claim 1 the fluid containing the mixed together components to be separated based upon the difference in density of the mixed together components;

continuously flowing the components in the fluid to the rotor through an input tube connected to the input port while the rotor is spinning about a centrifugal axis of rotation;

separating the components in the fluid into fractions based upon the difference in density of the mixed together components with the use of centrifugal force when the rotor is spinning;

collecting components having i) a first density via a first tube connected to the output port at the first end on the rotor, ii) a second density via a second tube connected to the output port at the second end on the rotor, iii) a third density via a third tube connected to the output port at the junction on the rotor and iv) a fourth density via a fourth tube connected to the output port between the input port and the output port at the first end.

10. The method of claim 9 wherein the components having a first density comprise high density sub-micron particles that have a density greater than the components with a second density, a third density or a fourth density.

11. The method of claim 10 wherein the high density sub-micron particles are functionalized to capture a first component from the components mixed together in the fluid.

12. The method of claim 9 wherein the fluid is blood.

13. The method of claim 12 wherein the components having a first density includes exosomes or oncosomes.

14. The method of claim 12 wherein the components having a second density include plasma.

15. The method of claim 12 wherein components having a third density includes buffy coat with or without circulating tumor cells.

16. The method of claim 12 wherein the components having a fourth density include red blood cells.

17. The method of claim 9 wherein the fluid is supplied to the rotor via the input tube by a pump.

18. The method of claim 9 wherein the components collected from the first tube, the second tube, or the fourth tube are pumped from the rotor to a reservoir.

19. The method of claim 18 wherein the reservoir is an animal or a container.

20. The method of claim 19 wherein the animal is a human.