Systems and methods of lipoprotein size fraction assaying

• US 20070202008A1
• Filed: 02/28/2006
• Published: 08/30/2007
• Est. Priority Date: 02/28/2006
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Schembri, Carol, Tom-Moy, May
• Application Number:
  US11/364,267
• Publication Number:
  US 20070202008A1
• Time in Patent Office: Days
• US Class Current: 422/57
• CPC Class Codes: G01N 33/48721 Investigating individual macromolecules, e.g. by translocation through nanopores Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

Systems and methods for nanopore flow cells are provided.

Claims

1. A nanopore analysis system, comprising:

a nanopore flow cell comprising

a first structure that separates two independent adjacent pools of a medium,

a first nanopore aperture through the first structure, the first nanopore aperture dimensioned to allow fluid communication between the two independent adjacent pools, and

an electrode adjacent and in electrical communication with the first nanopore aperture; and

a detection system designed to detect the size of the lipoproteins translocated through the first nanopore aperture.

2. The nanopore analysis system of claim 1, wherein the first nanopore aperture is approximately 100 nm across.

3. The nanopore analysis system of claim 1, wherein the first nanopore aperture is approximately 4 nm to 100 nm across.

4. The nanopore analysis system of claim 1, wherein the lipoprotein sizes detected correlate to at least one of the following types of lipoproteins:

VLDL (very low density lipoprotein), IDL (intermediate density), LDL (low density), HDL (high density), and subclasses and combinations of each.

5. The nanopore analysis system of claim 1, further comprising a second structure adjacent the first structure,

wherein the second structure comprises a second aperture of a different size than the first aperture, and

wherein the first aperture and the second aperture are in fluid communication with each other.

6. The nanopore analysis system of claim 1, further comprising a plurality of structures adjacent and in line with the first structure,

wherein each one of the plurality of structures comprises an aperture of a different size than the first aperture and the other apertures of the plurality of structures, and

wherein the first aperture and the apertures of the plurality of structures are in fluid communication with each other.

7. The nanopore analysis system of claim 1, wherein surfaces of the first nanopore aperture have a substantially neutral charge.

8. The nanopore analysis system of claim 1, wherein surfaces of the nanopore aperture are treated via atomic layer deposition, molecular layer deposition or chemically modified.

9. The nanopore analysis system of claim 8, wherein the surfaces of the nanopore aperture are treated with layers that are at least one of the following:

organic, inorganic, or combinations thereof.

10. A method for analyzing a lipoprotein, comprising:

providing a nanopore analysis system;

introducing a target lipoprotein to a nanopore flow cell in the nanopore analysis system;

applying a voltage gradient to the nanopore analysis system;

translocating the target lipoprotein through a nanopore aperture in the nanopore analysis system; and

monitoring a signal corresponding to the movement of the target lipoprotein with respect to the nanopore aperture.

11. The method of claim 10, wherein the nanopore aperture is approximately 4 nm to 100 nm across.

12. The method of claim 10, further comprising determining the size of the lipoprotein from the monitored signal corresponding to the movement of the target lipoprotein with respect to the nanopore aperture.

13. The method of claim 12, wherein the determined size of the lipoprotein corresponds to at least one of the following types of lipoproteins:

VLDL (very low density lipoprotein), IDL (intermediate density), LDL (low density), HDL (high density), and subclasses and combinations of each.

14. The method of claim 10, wherein the nanopore analysis system comprises a plurality of apertures in series, wherein the size of each aperture is progressively smaller than the preceding aperture.

15. The method of claim 10, further comprising treating surfaces of the nanopore flow cell to render the surfaces of substantially neutral charge.

16. The method of claim 10, further comprising slowing the rate of translocation of the lipoprotein through the aperture.

17. The method of claim 16, further comprising slowing the rate of translocation of the lipoprotein through the aperture to a rate at which the lipoprotein interacts with a surface of the aperture.

18. An array for size fractioning of lipoproteins, the array comprising:

a structure including a first layer fluidly coupled to a second layer, the first layer comprising

a first surface exposed to a first pool of fluid into which a sample of lipoproteins can be introduced, and

a second surface exposed to a second pool of fluid into which lipoproteins can be translocated;

a plurality of nanopores through the first layer;

electrodes associated with each nanopore; and

a second layer, wherein the first layer and the second layer form part of an enclosure for the second pool.

19. An array for size fractioning of lipoproteins, the array comprising:

a plurality of structures;

an associated membrane disposed in each structure; and

a plurality of nanopores disposed through each membrane, wherein each membrane comprises nanopores that are of a different size than nanopores of membrane(s) disposed adjacent it; and

wherein each nanopore is associated with a specific region, and wherein the regions of each membrane are aligned.

20. The array of claim 19 wherein reservoirs are disposed between the membranes, wherein the reservoirs are configured to collect or retain a lipoprotein-containing fluid.