IP Library Granted Patent US 10,570,439
Granted Patent B2
US 10,570,439 · App. 15/240,960 · Granted Feb 25, 2020

Sample concentration devices

Inventors: Keith A. Oberg (Camarillo, CA); Anthony Spence (Camarillo, CA); Ivan Rueda (Camarillo, CA); Mark D. Dobbs (Camarillo, CA); Milton Lee (Camarillo, CA)
Assignees: Monolythix, Inc.; Alfred E. Mann Foundation for Scientific Research
C12Q1/6806B01L3/5023G01N1/405B01L2200/026B01L2300/069B01L2300/0832B01L2300/12B01L2400/0406
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Quick Facts
Patent No.
US 10,570,439
App. No.
15/240,960
Granted
Feb 25, 2020
Kind
B2
Abstract

The present disclosure relates to a concentrator for concentrating, purifying or otherwise isolating one or more target analytes in a fluid matrix, and related methods, using self-wicking materials, such as monoliths. The present disclosure can be used as a point-of need sample preparation device. The self-contained device can be used for the extraction and concentration of specific target molecules, such as nucleic acids.

Claims (86)

1. A method for concentrating a negatively charged analyte in a fluid matrix, the method comprising:

providing an accumulator comprising a first self-wicking porous polymer monolith, the accumulator having:

a plurality of interface surfaces;

an accumulator fluid capacity volume (Vac); and

an affinity for negatively charged analyte;

providing a sink comprising a second self-wicking material, the sink having:

an interface surface configured for fluidic communication with any one of the plurality of interface surfaces of the accumulator; and

a sink fluid capacity volume (Vfs), wherein the sink fluid capacity volume (Vfs) is greater than the accumulator fluid capacity volume (Vac);

coupling a selected one of the plurality of interface surfaces of the accumulator to the interface surface of the sink;

wicking the fluid matrix containing the negatively charged analyte into the accumulator through any other interface surface of the accumulator;

capturing the negatively charged analyte in the accumulator by electrostatic attraction;

wicking the fluid matrix in excess of the accumulator fluid capacity volume (Vac) from the accumulator into the sink;

uncoupling the accumulator from the sink; and

eluting the negatively charged analyte from the accumulator without using a wash fluid to remove fluid matrix out of the accumulator.

2. The method of claim 1 , wherein the first self-wicking porous polymer monolith has a self-wicking rate of at least 1 cm.

3. The method of claim 1 , wherein the second self-wicking material is a porous polymer monolith.

4. The method of claim 1 , wherein the second self-wicking material has a self-wicking rate of at least 1.8 cm.

5. The method of claim 1 , further comprising:

retaining the excess fluid matrix in the sink.

6. The method of claim 1 , wherein the coupling of the accumulator and the sink comprises compressing the accumulator and sink together to form a mechanical junction.

7. The method of claim 1 , wherein eluting comprises:

coupling the elution fluid source to any selected interface surface of the accumulator wherein the elution fluid source and the selected interface surface of the accumulator are in fluid communication;

introducing an elution fluid having an elution fluid volume (Vef) from the elution fluid source into the accumulator through the selected interface surface of the accumulator, wherein the elution fluid volume (Vef) is greater than the accumulator fluid capacity volume (Vac), and wherein the elution fluid releases the analyte from the accumulator; and

collecting the negatively charged analyte from any other interface surface of the accumulator.

8. The method of claim 1 , wherein eluting comprises:

providing a matrix absorber comprising a third self-wicking material, the matrix absorber having:

an interface surface,

a bypass channel with an outlet, and

a matrix absorber fluid capacity volume (Vma), wherein the matrix absorber fluid capacity volume (Vma) is smaller than or equal to the accumulator fluid capacity volume (Vac);

coupling the interface surface of the matrix absorber to any selected interface surface of the accumulator, wherein the interface surface of the matrix absorber and the selected interface surface of the accumulator are in fluid communication;

providing an elution fluid source;

coupling the elution fluid source to any other interface surface of the accumulator wherein the elution fluid source and the any other interface surface of the accumulator are in fluid communication;

introducing an elution fluid having an elution fluid volume (Vef) from the elution fluid source into the accumulator through the any other interface surface of the accumulator, wherein the elution fluid volume (Vef) is greater than the accumulator fluid capacity volume (Vac), and wherein the elution fluid releases the analyte from the accumulator; and

collecting the analyte from the bypass channel outlet of the matrix absorber.

9. The method of claim 1 , wherein eluting comprises:

providing a matrix absorber comprising a third self-wicking material, the matrix absorber having:

an interface surface,

a bypass channel with an outlet, and

a matrix absorber fluid capacity volume (Vma), wherein the matrix absorber fluid capacity volume (Vma) is smaller than or equal to the accumulator fluid capacity volume (Vac);

coupling the interface surface of the matrix absorber to any selected interface surface of the accumulator, wherein the interface surface of the matrix absorber and the selected interface surface of the accumulator are in fluid communication;

providing an elution fluid source;

coupling the elution fluid source to any other interface surface of the accumulator wherein the elution fluid source and the any other interface surface of the accumulator are in fluid communication;

introducing a first portion of an elution fluid having a first elution fluid volume (Vef 1 ) from the elution fluid source into the accumulator through the any other interface surface of the accumulator, wherein the first elution fluid volume (Vef 1 ) is less than the accumulator fluid capacity volume (Vac),

introducing a second portion of an elution fluid having a second elution fluid volume (Vef 2 ) from the elution fluid source into the accumulator through the any other interface surface of the accumulator, wherein the first elution fluid volume (Vef 1 )+second elution fluid volume (Vef 2 ) is greater than the accumulator fluid capacity volume (Vac), and wherein the elution fluid releases the analyte from the accumulator; and

collecting the analyte from the bypass channel outlet of the matrix absorber.

10. The method of claim 9 , wherein the first portion of the elution fluid introduced into the accumulator displaces a first volume of fluid from the accumulator to the matrix absorber wherein the first volume of displaced fluid contains less than about 10% of the analyte contained in the accumulator.

11. The method of claim 9 , wherein the second portion of the elution fluid introduced into the accumulator displaces a second volume of fluid from the accumulator through the output of the matrix absorber, wherein the second volume of displaced fluid contains more than about 50% of the analyte contained in the accumulator.

12. The method of claim 1 , wherein at least a portion of the accumulator surface is sealed to prevent the passage of fluid out of the accumulator.

13. A concentrator for concentrating a negatively charged analyte in a fluid matrix, the concentrator comprising:

an accumulator comprising a first self-wicking porous polymer monolith, the accumulator having:

a plurality of interface surfaces;

an accumulator fluid capacity volume (Vac); and

an affinity for the negatively charged analyte by electrostatic attraction;

a sink comprising a second self-wicking material, the sink having:

at least one interface surface configured for fluidic communication with any one of the plurality of interface surfaces of the accumulator; and

a sink fluid capacity volume (Vfs), wherein:

the sink fluid capacity volume (Vfs) is greater than the accumulator fluid capacity volume (Vac);

the at least one interface surface of the sink and a selected one of the plurality of interface surfaces of the accumulator are coupled together in fluidic communication; and

the sink is configured to facilitate wicking of the fluid matrix in excess of accumulator fluid capacity (Vac) from the accumulator into the sink.

14. The concentrator of claim 13 , wherein the accumulator is a tapered cylinder shape.

15. The concentrator of claim 13 , wherein the second self-wicking material is a porous polymer monolith.

16. The concentrator of claim 13 , wherein the coupling between the accumulator and sink comprises a mechanical junction.

17. The concentrator of claim 13 , further comprising a housing, wherein the housing is configured to form a fluid-tight mechanical seal with a surface of the accumulator and having openings at one or more of the plurality of interface surfaces of the accumulator.

18. The concentrator of claim 17 , wherein the housing is covalently bonded to the first self-wicking porous polymer monolith.

19. The concentrator of claim 17 , wherein the housing has a hollow tapered cylinder shape.

20. The concentrator of claim 17 , wherein the housing further comprises an external port at one of the interface surfaces of the accumulator for receiving fluids.

21. The concentrator of claim 13 , further comprising an elution fluid dispenser, the elution fluid dispenser having:

an elution fluid reservoir; and

an elution fluid pressurizer;

wherein the elution fluid dispenser is configured to attach to the external port of the housing and to establish fluid communication between the elution fluid reservoir and one of the at least one interface surface of the accumulator.

22. The concentrator of claim 13 , further comprising a cutter, wherein the cutter is configured to separate the accumulator and the sink, wherein upon separation the accumulator and sink are no longer in fluid communication.

23. The concentrator of claim 13 , further comprising a matrix absorber, the matrix absorber comprising a third self-wicking material, the matrix absorber having:

an interface surface,

a bypass channel with an outlet, and

a matrix absorber fluid capacity volume (Vma), wherein the matrix absorber fluid capacity volume (Vma) is smaller than or equal to the accumulator fluid capacity volume (Vac);

wherein the interface surface of the matrix absorber is configured for fluid communication with any interface surface of the accumulator.

24. The method of claim 1 , wherein the negatively charged analyte comprises at least one of: lipid-membrane fragments, DNA, nucleic acids and proteins.

25. The method of claim 1 , wherein the accumulator can capture and retain DNA from the fluid matrix.

26. The method of claim 1 , wherein the accumulator comprises amino groups to capture the negatively charged analyte.

27. The method of claim 26 , wherein the eluting releases the negatively charged analyte from the accumulator by deprotonating the amino groups on the accumulator and thereby eliminating the electrostatic attraction between the amino groups and the negatively charged analyte.

28. The method of claim 1 , wherein the eluting disrupts the electrostatic attraction between the negatively charged analyte and the accumulator.

29. The concentrator of claim 13 , wherein the negatively charged analyte comprises at least one of: lipid-membrane fragments, DNA, nucleic acids and proteins.

30. The concentrator of claim 13 , wherein the accumulator can capture and retain DNA from the fluid matrix.

31. The concentrator of claim 13 , wherein the accumulator comprises amino groups to capture negatively charged analyte.

32. The concentrator of claim 31 , wherein the elution fluid is formulated to release the negatively charged analyte from the accumulator by deprotonating the amino groups on the accumulator and thereby eliminating the electrostatic attraction between the amino groups and the negatively charged analyte.

33. The concentrator of claim 13 , wherein the elution fluid is formulated to disrupt the electrostatic attraction between the negatively charged analyte and the accumulator.

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Jan 9, 2020
From: THE ALFRED E. MANN FOUNDATION FOR SCIENTIFIC RESEARCH
To: MONOLYTHIX, INC.
Reel/Frame 051467/0818 →
RELEASE OF SECURITY INTEREST Recorded Dec 18, 2019
From: THE ALFRED E. MANN FOUNDATION FOR SCIENTIFIC RESEARCH
To: MONOLYTHIX, INC.
Reel/Frame 051522/0428 →
SECURITY INTEREST Recorded Mar 28, 2017
From: MONOLYTHIX, INC.
To: THE ALFRED MANN FOUNDATION FOR SCIENTIFIC RESEARCH
Reel/Frame 041767/0535 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 6, 2016
From: OBERG, KEITH A; SPENCE, ANTHONY; RUEDA, IVAN; DOBBS, MARK D; LEE, MILTON
To: MONOLYTHIX, INC.
Reel/Frame 039970/0738 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 30, 2016
From: OBERG, KEITH A; SPENCE, ANTHONY; RUEDA, IVAN; DOBBS, MARK D; LEE, MILTON
To: MONOLYTHIX, INC.
Reel/Frame 039584/0874 →
Continuity (2)
Provisional Application 62206749 · Aug 18, 2015
Related Publication 20170051273A1 · Feb 23, 2017