IP Library › Granted Patent US 11,291,931
Granted Patent B2
US 11,291,931 · App. 16/004,874 · Granted Apr 5, 2022

Method and system for buoyant separation

Inventors: Brandon H. McNaughton (Ann Arbor, MI); John G. Younger (Ann Arbor, MI); Leo Ostruszka (Ann Arbor, MI); Jonathan Roussey (Ann Arbor, MI); Gene Parunak (Ann Arbor, MI); Aaron Kehrer (Ann Arbor, MI)
Assignee: Akadeum Life Sciences, Inc.
B01D21/0084B01D21/2433B01D21/262B01L3/5021B01L2200/026B01L2200/0652B01L2400/06G01N33/491
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Quick Facts
Patent No.
US 11,291,931
App. No.
16/004,874
Granted
Apr 5, 2022
Kind
B2
Abstract

A method and system for buoyant separation of a target constituent of a sample, the method comprising: at a process chamber, combining a volume of substrates having a first density with the sample, thereby producing a population of target-bound complexes comprising the target constituent bound to at least a portion of the volume of substrates; within the process chamber, physically separating the population of target-bound complexes from the sample based upon interaction between the volume of substrates and an applied force; aggregating the population of target-bound complexes at a collection region of the process chamber; extracting the population of target-bound complexes from the process chamber; and processing the target constituent from the population of target-bound complexes for further analysis.

Claims (38)

1. A method for buoyant separation of a set of target constituents of a sample comprising:

at a process chamber defining a single cavity, receiving:

the sample comprising the set of target constituents and a set of non-target constituents, wherein bulk fluid of the sample has a first density;

a volume of buoyant glass microbubble substrates having a second density, the second density less than the first density, wherein the buoyant glass microbubble substrates are configured to bind to at least a portion of the set of target constituents, and wherein the buoyant glass microbubble substrates and the set of target constituents are received at the process chamber at a volume ratio between 1:2 and 5:1;

a separation buffer;

thereby producing a set of target-bound complexes;

within the process chamber, reducing a distance between target-bound complexes of the set of target-bound complexes, thereby increasing a speed at which the set of target-bound complexes separate from a remainder of the bulk fluid of the sample;

within the process chamber, spatially separating the set of target-bound complexes from the remainder of the bulk fluid of the sample, wherein spatially separating comprises concentrating the set of target-bound complexes at a superior region of the process chamber;

removing the set of target-bound complexes from the superior region of the process chamber; and

processing the set of non-target constituents in the process chamber.

2. The method of claim 1 , further comprising coating each of the buoyant glass microbubble substrates with aminosilane.

3. The method of claim 2 , further comprising functionalizing the surface of each buoyant glass microbubble substrate with a set of biomolecules configured to bind to at least a portion of the set of target constituents after the coating of each of the buoyant glass microbubble substrates with aminosilane.

4. The method of claim 1 , wherein the process chamber has a non-decreasing diameter along a total length of the process chamber from an inferior-most point of the process chamber to a superior-most point of the process chamber.

5. The method of claim 4 , wherein the process chamber comprises a centrifuge tube.

6. The method of claim 1 , wherein each buoyant glass microbubble substrate of the volume of buoyant glass microbubble substrates has a diameter less than 30 micrometers.

7. The method of claim 6 , wherein the diameter is between 10 and 20 micrometers.

8. The method of claim 1 , wherein reducing the distance comprises adjusting an orientation of the process chamber.

9. The method of claim 8 , wherein adjusting the orientation of the process chamber comprises centrifuging the process chamber along an axis arranged non-parallel to a long axis of the process chamber.

10. The method of claim 8 , wherein the applied change in orientation of the process chamber comprises tilting the process chamber.

11. The method of claim 1 , further comprising mixing the sample and the volume of buoyant glass microbubble substrates within the single cavity with a pipette.

12. The method of claim 1 , wherein receiving the volume of buoyant glass microbubble substrates at the process chamber comprises receiving the volume of buoyant glass microbubble substrates from a storage buffer configured to maintain a stability of the buoyant glass microbubble substrates.

13. The method of claim 1 , wherein removing the target-bound complexes from the superior region of the process chamber comprises aspirating the target-bound complexes from the superior region.

14. A method for buoyant separation of a set of target constituents of a sample, the method comprising:

at a process chamber, receiving:

the sample comprising the set of target constituents and a set of non-target constituents, wherein bulk fluid of the sample has a first density;

a volume of buoyant microbubble substrates having a second density, the second density less than the first density, wherein the buoyant microbubble substrates are configured to bind with at least a portion of the set of target constituents;

a separation buffer;

thereby producing a set of target-bound complexes, wherein the volume of buoyant microbubble substrates and the set of target constituents are received at the process chamber at a ratio between 1:2 and 5:1;

within the process chamber, spatially separating the set of target-bound complexes from the remainder of the bulk fluid of the sample, wherein spatially separating comprises concentrating the set of target-bound complexes at a superior region of the process chamber;

removing the set of target-bound complexes from the superior region of the process chamber; and

processing the set of non-target constituents in the process chamber.

15. The method of claim 14 , wherein each buoyant microbubble substrate of the volume of buoyant microbubble substrates comprises at least one of a plastic, lipid, and glass.

16. The method of claim 15 , wherein each buoyant microbubble substrate of the volume of buoyant microbubble substrates comprises glass.

17. The method of claim 14 , wherein the process chamber defines a single cavity.

18. The method of claim 14 , wherein the ratio is between 1:1 and 2.5:1.

19. The method of claim 14 , further comprising within the process chamber, reducing a distance between target-bound complexes of the set of target-bound complexes, thereby increasing a speed at which the set of target-bound complexes separate from a remainder of the bulk fluid of the sample.

20. The method of claim 19 , wherein reducing a distance comprises adjusting an orientation of the process chamber.

21. The method of claim 14 , wherein processing the set of non-target constituents in the process chamber comprises receiving a second buffer at the process chamber after removing the target-bound complexes.

Assignments (2)
SECURITY INTEREST Recorded Jun 22, 2023
From: AKADEUM LIFE SCIENCES, INC.
To: WTI FUND X, INC.
Reel/Frame 064035/0428 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 13, 2018
From: MCNAUGHTON, BRANDON H.; YOUNGER, JOHN G.; OSTRUSZKA, LEO; ROUSSEY, JONATHAN; PARUNAK, GENE; KEHRER, AARON
To: AKADEUM LIFE SCIENCES, INC.
Reel/Frame 046626/0417 →
Continuity (6)
Continuation In Part 14969446 · Dec 15, 2015
Provisional Application 62092019 · Dec 15, 2014
Provisional Application 62189518 · Jul 7, 2015
Provisional Application 62616647 · Jan 12, 2018
Provisional Application 62517543 · Jun 9, 2017
Related Publication 20180290077A1 · Oct 11, 2018
Cited By (2)
US 12,196,754 US 12,383,893