# US 7,741,104 B2 · Capillary array and related methods

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- Number: US 7,741,104 B2
- Document ID: US7741104B2
- Status: Granted
- Kind: B2
- Application number: 11/293,047
- Filed: 2005-12-01
- Published: 2006-07-20
- Granted: 2010-06-22
- Earliest claimed: 2000-08-31
- Assignees: The Regents of the University of California
- Inventors: Mack J Fulwyler; Joe W Gray
- Web page: https://patentgrep.com/patent/US7741104B2

## CPC

- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- 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)}
- B01J 2219/00479: Means for mixing reactants or products in the reaction vessels
- B01J 2219/00511: Walls of reactor vessels
- B01J 2219/0052: in the shape of elongated tubes
- B01J 2219/00605: the compounds being directly bound or immobilised to solid supports
- B01J 2219/0061: The surface being organic
- B01J 2219/00612: the surface being inorganic
- B01J 2219/00621: by physical means, e.g. trenches, raised areas
- B01J 2219/00626: Covalent
- B01J 2219/00628: Ionic
- B01J 2219/0063: Other, e.g. van der Waals forces, hydrogen bonding
- B01J 2219/00637: by coating it with another layer
- B01J 2219/00641: the porous medium being continuous, e.g. porous oxide substrates
- B01J 2219/00657: One-dimensional arrays
- B01J 2219/00722: Nucleotides
- B01L 2200/0673: Handling of plugs of fluid surrounded by immiscible fluid
- B01L 2300/0636: Integrated biosensor, microarrays
- B01L 2300/0816: Cards, e.g. flat sample carriers usually with flow in two horizontal directions
- B01L 2300/0838: Capillaries
- B01L 2400/0406: capillary forces
- B01L 2400/0415: electrical forces, e.g. electrokinetic
- B01L 2400/0421: electrophoretic flow
- B01L 2400/0487: fluid pressure, pneumatics
- Y10S 436/807: Apparatus included in process claim, e.g. physical support structures
- Y10T 436/117497: with a continuously flowing sample or carrier stream
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## 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

### Claim 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.

### Claim 2 (depends on 1)

The device of claim 1, wherein said capillary tube has a cross-sectional diameter of about 100 μm or less.

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1, 3)

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

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

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

### Claim 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 μm 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.

### Claim 11 (depends on 10)

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

### Claim 12 (depends on 10)

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.

### Claim 13 (depends on 10)

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