Method of synthesis and testing of combinatorial libraries using microcapsules

• US 7,718,578 B2
• Filed: 09/29/2005
• Issued: 05/18/2010
• Est. Priority Date: 03/31/2003
• Status: Active Grant

• Current Assignee: UK Research and Innovation
• Original Assignee: Medical Research Council (Government of United Kingdom)
• Inventors: Griffiths, Andrew David, Abell, Chris, Mastrobattista, Enrico, Hollfelder, Florian
• Primary Examiner(s): Wessendorf; Teresa D.
• Application Number:
  US11/238,257
• Publication Number:
  US 20060154298A1
• Time in Patent Office: 1,692 Days
• Field of Search: 506/23, 506/9, 506/7
• US Class Current: 506/23
• 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 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00743 Cells
• CPC Class Codes: B01J 2219/00835 Comprising catalytically active material
• CPC Class Codes: B01J 2219/0086 Dimensions of the flow channels
• CPC Class Codes: B01J 2219/00894 More than two inlets
• CPC Class Codes: B01J 2219/00903 Segmented flow
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 1/047 Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C12N 15/1075 : by coupling phenotype to genotype, not provided for in other groups of this subclass
• CPC Class Codes: C40B 20/04 : Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
• CPC Class Codes: C40B 30/04 : by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 50/08 : Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
• CPC Class Codes: G01N 33/5432 : Liposomes or microcapsules

Abstract

The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalizing two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reactions between primary compounds from different sets. The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalized into the microcapsules.

Claims

1. A method of forming a small molecule compound comprising:

providing at least a first aqueous fluid comprising at least a first small molecule compound having a molecular weight of less than 500 Daltons wherein said first small molecule compound is an amine with a difluoromethylene phosphonate moiety;

providing at least a second aqueous fluid comprising at least a second small molecule compound having a molecular weight of less than 500 Daltons wherein said second small molecule compound is an aldehyde with a difluoromethylene phosphonate moiety;

encapsulating said at least first small molecule compound into at least a first aqueous microcapsule within an immiscible fluorocarbon oil;

encapsulating said at least second small molecule compound into at least a second aqueous microcapsule within an immiscible fluorocarbon oil; and

fusing said at least first and said at least second aqueous microcapsules, thereby causing a chemical reaction between said at least first and at least second small molecule compounds to form at least a third small molecule compound.

2. The method of claim 1, wherein said at least first small molecule compound is attached to a microbead.

3. The method of claim 1, wherein said at least second small molecule compound is attached to a microbead.

4. The method of claim 1, further comprising isolating said at least third small molecule compound.

5. The method of claim 1, further comprising identifying said at least third small molecule compound.

6. The method of claim 5, wherein said at least third small molecule compound is identified by its optical properties.

7. The method of claim 1, wherein said at least first small molecule compound comprises at least a first label and said at least second small molecule compound comprises at least a second label, wherein said at least first and said at least second labels are different.

8. The method of claim 1, wherein said at least second aqueous microcapsule comprises no more than one said at least second small molecule compound.