Title: Replica amplification of nucleic acid arrays

Abstract

Disclosed are improved methods of making and using immobilized arrays of nucleic acids, particularly methods for producing replicas of such arrays. Included are methods for producing high density arrays of nucleic acids and replicas of such arrays, as well as methods for preserving the resolution of arrays through rounds of replication. Also included are methods which take advantage of the availability of replicas of arrays for increased sensitivity in detection of sequences on arrays. Improved methods of sequencing nucleic acids immobilized on arrays utilizing single copies of arrays and methods taking further advantage of the availability of replicas of arrays are disclosed. The improvements lead to higher fidelity and longer read lengths of sequences immobilized on arrays. Methods are also disclosed which improve the efficiency of multiplex PCR using arrays of immobilized nucleic acids.

Inventors:

Church, George M ^[1]; Mitra, Robi D ^[2]

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+ Show Inventor Affiliations

1. Brookline, MA
2. Chestnut Hill, MA

Issue Date:

2010-08-31

Research Org.:

President and Fellows of Harvard College (Cambridge, MA)

Sponsoring Org.:

USDOE

OSTI Identifier:

1013607

Patent Number(s):

7785790

Application Number:

11/745,806

Assignee:

President and Fellows of Harvard College (Cambridge, MA)

Patent Classifications (CPCs):

C - CHEMISTRY C12 - BIOCHEMISTRY C12Q - MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS

B - PERFORMING OPERATIONS B01 - PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL B01J - CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY

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C - CHEMISTRY C12 - BIOCHEMISTRY C12Q - MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS

C12Q2565/515 - characterised by the interaction between or sequential use of two or more arrays

B - PERFORMING OPERATIONS B01 - PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL B01J - CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY

B01J2219/00722 - Nucleotides
B01J2219/00641 - the porous medium being continuous, e.g. porous oxide substrates
B01J2219/00702 - Processes involving means for analysing and characterising the products

C - CHEMISTRY C12 - BIOCHEMISTRY C12Q - MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS

C12Q1/6874 - involving nucleic acid arrays, e.g. sequencing by hybridisation
C12Q1/6837 - using probe arrays or probe chips

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES

C07K1/047 - {Simultaneous synthesis of different peptide species

B - PERFORMING OPERATIONS B01 - PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL B01J - CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY

B01J2219/00657 - One-dimensional arrays

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DOE Contract Number:  

FG02-87ER60565

Resource Type:

Patent

Country of Publication:

United States

Language:

English