High-Throughput Droplet Digital PCR System for Absolute Quantitation of DNA Copy Number

Высокопроизводительная система капельной цифровой ПЦР для абсолютного количественного определения числа копий ДНК
Benjamin J. Hindson, Kevin D. Ness, Donald A Masquelier, Phillip Belgrader, Nicholas J. Heredia, Anthony J. Makarewicz, Isaac J. Bright, Michael Y. Lucero, Amy L. Hiddessen, Tina C. Legler, Tyler K. Kitano, Michael R. Hodel, Jonathan F. Petersen, Paul W. Wyatt, Erin R. Steenblock, Pallavi Shah, Luc Bousse, Camille Troup, Jeffrey C. Mellen, Dean K. Wittmann, Nicholas G. Erndt, Thomas H. Cauley, Ryan T. Koehler, Austin P. So, Simant Dube, Klint A. Rose, Luz Montesclaros, Shenglong Wang, D. P. Stumbo, Shawn P. Hodges, Steven Romine, Fred P. Milanovich, Helen White, John F. Regan, George Karlin‐Neumann, Christopher M. Hindson, Serge Saxonov, Bill W. Colston
2011-10-28

absolute DNA quantitationcell-free fetal DNAcopy number variationdroplet digital PCRrare allele detection
Digital PCR enables the absolute quantitation of nucleic acids in a sample. The lack of scalable and practical technologies for digital PCR implementation has hampered the widespread adoption of this inherently powerful technique. Here we describe a high-throughput droplet digital PCR (ddPCR) system that enables processing of ~2 million PCR reactions using conventional TaqMan assays with a 96-well plate workflow. Three applications demonstrate that the massive partitioning afforded by our ddPCR system provides orders of magnitude more precision and sensitivity than real-time PCR. First, we show the accurate measurement of germline copy number variation. Second, for rare alleles, we show sensitive detection of mutant DNA in a 100,000-fold excess of wildtype background. Third, we demonstrate absolute quantitation of circulating fetal and maternal DNA from cell-free plasma. We anticipate this ddPCR system will allow researchers to explore complex genetic landscapes, discover and validate new disease associations, and define a new era of molecular diagnostics.
1
A high-throughput droplet digital PCR system processes approximately 2 million PCR reactions using conventional TaqMan assays in a 96-well plate workflow.
2
Massive sample partitioning provides orders-of-magnitude greater precision and sensitivity than real-time PCR.
3
The platform enables absolute quantitation of circulating fetal and maternal cell-free DNA in plasma.
4
The system accurately measures germline DNA copy-number variation.
5
The system detects rare mutant alleles in a 100,000-fold excess of wild-type DNA.

High-throughput droplet digital PCR (ddPCR) system and the DNA samples analyzed with it, including germline, rare mutant, and circulating fetal and maternal DNA

Absolute DNA copy-number quantitation and the system’s precision and sensitivity for measuring copy-number variation, detecting rare mutant alleles, and quantifying cell-free fetal and maternal DNA

Publication Details
Publication Date
2011-10-28
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Authors
Benjamin J. Hindson
Kevin D. Ness
Donald A Masquelier
Phillip Belgrader
Nicholas J. Heredia
Anthony J. Makarewicz
Isaac J. Bright
Michael Y. Lucero
Amy L. Hiddessen
Tina C. Legler
Tyler K. Kitano
Michael R. Hodel
Jonathan F. Petersen
Paul W. Wyatt
Erin R. Steenblock
Pallavi Shah
Luc Bousse
Camille Troup
Jeffrey C. Mellen
Dean K. Wittmann
Nicholas G. Erndt
Thomas H. Cauley
Ryan T. Koehler
Austin P. So
Simant Dube
Klint A. Rose
Luz Montesclaros
Shenglong Wang
D. P. Stumbo
Shawn P. Hodges
Steven Romine
Fred P. Milanovich
Helen White
John F. Regan
George Karlin‐Neumann
Christopher M. Hindson
Serge Saxonov
Bill W. Colston
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