METHODS FOR MANUFACTURING MOLECULAR ARRAYS

• US 20130096033A1
• Filed: 12/03/2012
• Published: 04/18/2013
• Est. Priority Date: 10/28/2011
• Status: Active Grant

• Current Assignee: Prognosys Biosciences Inc.
• Original Assignee: Prognosys Biosciences Inc.
• Inventors: Routenberg, David A.
• Granted Patent: US 9,012,374 B2
• Time in Patent Office: Days
• US Class Current: 506/26
• 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 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00382 Stamping
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/515 characterised by the interaction between or sequential use of two or more arrays
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 50/06 Biochemical methods, e.g. using enzymes or whole viable microorganisms
• CPC Class Codes: C40B 50/18 using a particular method of attachment to the solid support
• CPC Class Codes: C40B 60/12 for screening libraries

Abstract

The methods of the present invention provide methods for manufacturing a master substrate and methods for manufacturing replica arrays from the master substrate. The methods may be used, for example, directly to manufacture or “print” peptide arrays from a DNA array; however, the methods are applicable to a wide range of manufacturing applications for use any time multiple copies of an array needs to be printed.

Claims

1. A method of manufacturing an array of products on a replica array comprising:

providing a master substrate having partitioned reaction volumes;

generating products by one or more enzymatic processes in the partitioned reaction volumes; and

immobilizing the products from the partitioned reaction volumes from the master substrate on capture moieties disposed on a replica array that is in contact with the partitioned reaction volumes;

wherein partitioning of the reaction volumes prevents diffusion of products between them.

2. The method of claim 1, wherein the reaction volumes are partitioned by surface energetic barriers on the master substrate.

3. The method of claim 1, wherein the master substrate is a template array.

4. The method of claim 1, wherein there are at least 100 partitioned reaction volumes per square centimeter on the master substrate.

5. The method of claim 4, wherein there are at least 10,000 partitioned reaction volumes per square centimeter on the master substrate.

6. The method of claim 1, wherein at least 1000 different products from separate partitioned reaction volumes on the master substrate are arrayed on the replica array at a density of at least 1000 different products per square centimeter.

7. The method of claim 1, wherein at least a portion of each product from substantially all partitioned reaction volumes are arrayed on the replica array.

8. The method of claim 1, further comprising after the immobilizing step, the steps of removing the replica array;

sequentially furnishing one or more replica arrays comprising capture moieties; and

immobilizing the products from the partitioned reaction volumes from the master substrate on the capture moieties on the one or more replica arrays, wherein partitioning between products from separate partitioned reaction volumes is preserved.

9. The method of claim 1, further comprising replenishing or regenerating partitioned reaction volumes on the master substrate;

generating products by one or more enzymatic processes in the partitioned reaction volumes on the master substrate;

sequentially furnishing one or more replica arrays comprising capture moieties; and

immobilizing the products from the partitioned reaction volumes from the master substrate on the capture moieties on the one or more replica arrays, wherein partitioning between products from separate partitioned reaction volumes is preserved.

10. The method of claim 1, wherein at least one component of at least one of the enzymatic process is attached to the master substrate.

11. The method of claim 1, wherein the one or more enzymatic processes comprise one or more of replication, transcription or translation.

12. The method of claim 1, wherein the reaction volumes are partitioned by surface energetic barriers on the replica array.

13. The method of claim 1, wherein the reaction volumes are partitioned by the combination of surface energetic barriers on the master substrate and surface energetic barriers on the replica array.