Capillary array and related methods

• US 7,741,104 B2
• Filed: 12/01/2005
• Issued: 06/22/2010
• Est. Priority Date: 08/31/2000
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Fulwyler, Mack J, Gray, Joe W
• Primary Examiner(s): YU, MELANIE J
• Application Number:
  US11/293,047
• Publication Number:
  US 20060160162A1
• Time in Patent Office: 1,664 Days
• Field of Search: 436/518, 436/524, 436/525, 435/7.1, 435/283.1, 435/287.2, 435/288.3, 435/288.7, 422/50, 422/55, 422/68.1
• US Class Current: 435/287.2
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/0052 in the shape of elongated tubes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00628 Ionic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 33/558 : using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: Y10S 436/807 : Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream

Abstract

The invention provides methods and devices for detecting the presence of one or more target analytes in a sample employing a channel having affixed therein one or more binding partners for each target analyte. Assays are carried out by transporting the sample through the channel to each successive binding partner so that target analyte present in said sample binds to the corresponding binding partner. The sample is then transported beyond the binding partner(s), followed by detection of any target analyte bound to each binding partner. In one embodiment, binding efficiency is increased by the use of segmented transport, wherein a first bolus or bubble of a fluid that is immiscible with the sample precedes the sample during transport and a second bolus or bubble of a fluid that is immiscible with the sample follows the sample. Many configurations are possible for the device of the invention. A preferred device includes: a substrate with a channel formed in its surface, and a cover element that overlies and seals the channel. Binding partner(s) are affixed to the surface of the cover element facing the channel lumen.

Claims

1. A device for detecting the presence of a first target analyte in a sample, said device comprising a capillary tube comprising a wall and a lumen;

a first electrode projecting into the lumen;

a permeation layer overlying said first electrode, and a first binding partner for said first target analyte attached to said permeation layer;

a semipermeable tube which is inserted into the capillary tube, wherein the semipermeable tube encircles the first electrode and defines an annular space with the capillary wall; and

a second electrode located in the annular space between the semipermeable tube and the capillary wall.

2. The device of claim 1, wherein said capillary tube has a cross-sectional diameter of about 100 μ

m or less.

3. The device of claim 1, wherein at least about 100 different binding partners are affixed to distinct locations on said permeation layer.

4. The device of claim 1, wherein said first binding partner is selected from the group consisting of an antibody, a binding protein, and a nucleic acid.

5. The device of claim 1, wherein the permeation layer has a porosity that excludes one or more target analyte molecule(s).

6. The device of claim 1, wherein the permeation layer is hydrophilic.

7. The device of claims 1 or 3, wherein the semipermeable tube is not permeable to said target analyte(s).

8. The device of claim 1, wherein semipermeable tube is permeable to ions.

9. The device of claim 1, wherein said annular space comprises a conductive fluid.

10. A device for detecting the presence of a first target analyte in a sample, said device comprising

a capillary tube comprising a wall and a lumen, wherein said capillary tube has a cross-sectional diameter of about 100 μ

m or less;

a first electrode projecting into the lumen;

a permeation layer overlying said first electrode, wherein the permeation layer is hydrophilic and has a porosity that excludes said first target analyte molecule(s);

a first binding partner for said first target analyte attached to said permeation layer;

a semipermeable tube which is inserted into the capillary tube, wherein the semipermeable tube encircles the first electrode and defines an annular space with the capillary wall, wherein the semipermeable tube is not permeable to said first target analyte, and wherein the semipermeable tube is permeable to ions; and

a second electrode located in the annular space between the semipermeable tube and the capillary wall.

11. The device of claim 10, wherein at least about 100 different binding partners are affixed to distinct locations on said permeation layer.

12. The device of claim 10, wherein said first binding partner is selected from the group consisting of an antibody, a binding protein, and a nucleic acid.

13. The device of claim 10, wherein said annular space comprises a conductive fluid.