Capillary array-based sample screening

• US 20030096220A1
• Filed: 05/28/2002
• Published: 05/22/2003
• Est. Priority Date: 06/16/1997
• Status: Abandoned Application

• Current Assignee: Diversa Corporation (BASF SE)
• Original Assignee: Diversa Corporation (BASF SE)
• Inventors: Keller, Martin, Short, Jay M., Lafferty, William Michael
• Application Number:
  US10/156,878
• Publication Number:
  US 20030096220A1
• Time in Patent Office: Days
• US Class Current: 506/6
• 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 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/00479 Means for mixing reactants or products in the reaction vessels
• CPC Class Codes: B01J 2219/00481 by the use of moving stirrers within the reaction vessels
• CPC Class Codes: B01J 2219/00522 in a multiple parallel arrangement
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• 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 2219/00619 using hydrophilic or hydrophobic regions
• 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 2219/0063 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00686 Automatic
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/0074 : Biological products
• CPC Class Codes: B01J 2219/00743 : Cells
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/50857 : using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12N 15/1037 : Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
• CPC Class Codes: C12N 15/1055 : Protein x Protein interaction, e.g. two hybrid selection
• CPC Class Codes: C12Q 1/6811 : Selection methods for production or design of target specific oligonucleotides or binding molecules
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C40B 40/02 : Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries

Abstract

Provided are methods of screening and identification of bioactivities and bioactive molecules of interest using a capillary array system. More specifically, disclosed are methods of using optical detection and capillary array-based techniques for screening libraries and recovering bioactive molecules having a desired activity or a nucleic acid sequence encoding such bioactive molecules.

Claims

1. A method for identifying a bioactivity or biomolecule of interest, comprising:

(a) introducing a recombinant clone into a capillary tube of a capillary array, wherein each capillary tube of the capillary array comprises at least one wall defining a lumen for retaining the recombinant clone, and wherein the at least one wall is comprised of a material having a low refractive index;

(b) exposing the recombinant clone to conditions which induce a detectable signal; and

(c) detecting the detectable signal in the capillary tube to identify one or more capillaries containing the detectable signal thereby identifying the bioactivity or biomolecule of interest.

5. The method of claim 1, wherein each capillary tube in the array is separated from one another by a material with a low refractive index.

8. The method of claim 1, wherein each capillary tube of the capillary array comprises at least a first wall and a second wall wherein the first wall defines a lumen for retaining the substrate and the recombinant clone and is comprised of a material having a high refractive index and the second wall surrounds the first wall and is comprised of a material having a low refractive index, wherein the second wall is in contact with at least one other capillary tube second wall.

2. A method for identifying a bioactivity or biomolecule of interest, comprising:

(a) introducing a recombinant clone into a capillary tube of a capillary array, wherein each capillary tube of the capillary array comprises at least one wall defining a lumen for retaining the recombinant clone, and the at least one wall is comprised of a material having a low refractive index, and wherein the recombinant clone contains a substrate;

(b) exposing the recombinant clone to conditions which causes the substrate to produce a detectable signal; and

(c) detecting the detectable signal in the capillary tube to identify one or more capillaries containing the detectable signal thereby identifying the bioactivity or biomolecule of interest.

9. The method of claim 2, wherein each capillary tube of the capillary array comprises at least a first wall and a second wall wherein the first wall defines a lumen for retaining the substrate and the recombinant clone and is comprised of a material having a high refractive index and the second wall surrounds the first wall and is comprised of a material having a low refractive index, wherein the second wall is in contact with at least one other capillary tube second wall.

3. A method for identifying a bioactivity or biomolecule of interest, comprising:

(a) introducing a recombinant clone into a capillary tube of a capillary array, wherein each capillary tube of the capillary array comprises at least one wall defining a lumen for retaining the recombinant clone, and wherein the recombinant clone contains a substrate;

(b) exposing the recombinant clone to conditions which causes the substrate to produce a detectable signal; and

(c) detecting the detectable signal in the capillary tube to identify one or more capillaries containing the detectable signal thereby identifying the bioactivity or biomolecule of interest.

4. A method for identifying a bioactivity or biomolecule of interest, comprising:

(a) introducing a substrate labeled with a detectable molecule and a recombinant clone into a capillary tube of a capillary array, wherein each capillary tube of the capillary array comprises at least one wall defining a lumen for retaining the substrate and the recombinant clone and wherein each capillary tube in the array is separated from one another by a material with a low refractive index;

(b) culturing the capillary tube containing the substrate and the recombinant clone under conditions which allow interaction of the substrate and the recombinant clone to produce a detectable signal; and

(c) detecting the detectable signal in the capillary tube to identify one or more capillary tubes containing the detectable signal thereby identifying the bioactivity or biomolecule of interest.

7. The method of claim 4, wherein each capillary tube of the capillary array comprises at least a first wall and a second wall wherein the first wall defines a lumen for retaining the substrate and the recombinant clone and is comprised of a material having a high refractive index and the second wall surrounds the first wall and is comprised of a material having a low refractive index, wherein the second wall is in contact with at least one other capillary tube second wall.

6. A method for identifying a bioactivity or biomolecule of interest, comprising:

(a) introducing a recombinant clone containing a substrate into a capillary tube of a capillary array, wherein each capillary tube of the capillary array comprises at least one wall defining a lumen for retaining the recombinant clone and wherein each capillary tube in the array is separated from one another by a material with a low refractive index;

(b) exposing the recombinant clone to conditions which causes the substrate to produce a detectable signal; and

(c) detecting the detectable signal in the capillary tube to identify one or more capillary tubes containing the detectable signal thereby identifying the bioactivity or biomolecule of interest.

10. A method for identifying a compound of interest, comprising:

(a) introducing a sample containing a plurality of compounds into a capillary tube of a capillary array, wherein each capillary tube of the capillary array comprises at least one wall defining a lumen for retaining the sample, and the at least one wall is comprised of a material having a low refractive index, and wherein the recombinant clone contains a substrate;

(b) exposing the sample in the capillary tube to conditions which causes the compound of interest to produce a detectable signal; and

c) detecting the detectable signal in the capillary tube to identify one or more capillaries containing the detectable signal thereby identifying the compound of interest.