IP Library Granted Patent US 8,765,380
Granted Patent B2
US 8,765,380 · App. 13/618,334 · Granted Jul 1, 2014

Bead emulsion nucleic acid amplification

Inventors: Jan Berka (New Haven, CT); Yi-Ju Chen (New Haven, CT); John H. Leamon (Guilford, CT); Steve Lefkowitz (Branford, CT); Kenton L. Lohman (Guilford, CT); Vinod B. Makhijani (Guilford, CT); Jonathan M. Rothberg (Guilford, CT); Gary J. Sarkis (Guilford, CT); Maithreyn Srinivasan (Branford, CT); Michael P. Weiner (Guilford, CT)
Assignee: 454 Life Sciences Corporation
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Quick Facts
Patent No.
US 8,765,380
App. No.
13/618,334
Granted
Jul 1, 2014
Kind
B2
Abstract

Disclosed are methods for nucleic acid amplification wherein nucleic acid templates, beads, and amplification reaction solution are emulsified and the nucleic acid templates are amplified to provide clonal copies of the nucleic acid templates attached to the beads. Also disclosed are kits and apparatuses for performing the methods of the invention.

Claims (12)

1. A method for analyzing nucleic acid sequences comprising:

(a) delivering a plurality of molecules of a deoxyribonucleic acid into aqueous microreactors in a water-in-oil emulsion such that a plurality of aqueous microreactors comprise a single molecule of the deoxyribonucleic acid, a single bead capable of hybridizing the deoxyribonucleic acid, and reagents necessary to perform deoxyribonucleic acid amplification;

(b) amplifying the deoxyribonucleic acid in the microreactors to form amplified copies of said deoxyribonucleic acid bound to beads in the microreactors;

(c) determining the presence of amplified copies of said deoxyribonucleic acid bound to a bead.

2. The method of claim 1 wherein step (c) is accomplished using polymerase chain reaction.

3. The method of claim 1 , wherein a majority of the microcarriers include a single molecule of the deoxyribonucleic acid.

4. The method of claim 1 , wherein said reagents include a polymerase chain reaction solution further comprising nucleotide triphosphates, a thermostable polymerase, and a buffer compatible with polymerase chain reaction conditions.

5. The method of claim 1 , wherein said emulsion is heat stable.

6. The method of claim 1 , wherein amplification is carried out by a method selected from the group consisting of transcription-based amplification, rapid amplification of cDNA ends, continuous flow amplification, and rolling circle amplification.

7. The method of claim 1 , performed with at least 50,000 molecules of deoxyribonucleic acid.

8. The method of claim 1 , wherein between at least 1 to 20,000,000 copies of each deoxyribonucleic acid molecule are bound to each bead.

9. The method of claim 1 , further comprising, after step (b), the step of: separating the beads with amplified copies of the deoxyribonucleic acid thereon away from the beads that do not have amplified copies of the deoxyribonucleic acid bound.

Assignments (2)
CHANGE OF NAME Recorded Sep 19, 2012
From: 454 CORPORATION
To: 454 LIFE SCIENCES CORPORATION
Reel/Frame 028985/0398 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 18, 2012
From: BERKA, JAN; CHEN, YI-JU; LEAMON, JOHN H.; LEFKOWITZ, STEVE; LOHMAN, KENTON L.; MAKHIJANI, VINOD B.; ROTHBERG, JONATHAN M.; SARKIS, GARY J.; SRINIVASAN, MAITHREYAN; WEINER, MICHAEL P.
To: 454 CORPORATION
Reel/Frame 028976/0366 →
Continuity (11)
Continuation 13033240 · Feb 23, 2011
Continuation 11982095 · Oct 31, 2007
Continuation 10767899 · Jan 28, 2004
Provisional Application 60443471 · Jan 29, 2003
Provisional Application 60465071 · Apr 23, 2003
Provisional Application 60476313 · Jun 6, 2003
Provisional Application 60476504 · Jun 6, 2003
Provisional Application 60476592 · Jun 6, 2003
Provisional Application 60476602 · Jun 6, 2003
Provisional Application 60497985 · Aug 25, 2003
Related Publication 20130078638A1 · Mar 28, 2013