High-throughput droplet digital PCR system for absolute quantitation of DNA copy number
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Digital PCR provides an alternative approach for detecting gene expression when the amount of target RNA is low and approaching the limits of sensitivity of qPCR.
“Digital polymerase chain reaction (dPCR) provides an alternative approach for the detection of gene expression in the setting where the amount of target RNA is low and approaching the limits of sensitivity of qPCR (10).”
From Analysis of Extracellular RNA by Digital PCR (2014) · cites this paper as [10]
The Abstract says the droplet digital PCR system provides greater sensitivity than real-time PCR, and Results and Discussion reports detection of rare mutant DNA below the real-time PCR detection limit. The paper's examples concern DNA, however; these passages do not establish its use for detecting gene expression when target RNA is scarce. (LLM, conf=0.86)
Experimental — accuracy not yet measuredWhen an oversized transgene in AAV is truncated from the terminals, neither qPCR nor ddPCR, using a selected amplicon toward the end of the transgene, can accurately determine the titer of complete genomes, because the PCR replication cycle only considers the presence of the amplicon itself.
“When an oversized transgene in AAV is truncated from the terminals, neither qPCR nor ddPCR, using a selected amplicon toward the end of the transgene, can accurately determine the titer of complete genomes, as the PCR replication cycle only considers the presence of the amplicon itself, i.e., the DNA flanked by the primer sequences.25,83”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [83]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
dbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502 · see citing works
Presence of fetal DNA in maternal plasma and serum
Lo, Y. M. D., Corbetta, N., Chamberlain, P. F., Rai, V., Sargent, I. L., Redman, C. W., & Wainscoat, J. S. (1997) · The Lancet · doi:10.1016/s0140-6736(97)02174-0 · Cited by 3,129 · see citing works
Schouten, J. P. (2002) · Nucleic Acids Research · doi:10.1093/nar/gnf056 · Cited by 2,705 · see citing works
Vogelstein, B., & Kinzler, K. W. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.9236 · Cited by 1,770 · see citing works
The Influence of CCL3L1 Gene-Containing Segmental Duplications on HIV-1/AIDS Susceptibility
Gonzalez, E., Kulkarni, H. R., Bolivar, H., Mangano, A. M., Sanchez, R., Catano, G., Nibbs, R. J. B., Freedman, B. I., Quinones, M. P., Bamshad, M. J., et al. (2005) · Science · doi:10.1126/science.1101160 · Cited by 1,127 · see citing works
Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood
Fan, H. C., Blumenfeld, Y. J., Chitkara, U., Hudgins, L., & Quake, S. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808319105 · Cited by 1,110 · see citing works
Dressman, D. C., Yan, H., Traverso, G., Kinzler, K. W., & Vogelstein, B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1133470100 · Cited by 845 · see citing works
Personalized copy number and segmental duplication maps using next-generation sequencing
Alkan, C., Kidd, J. M., Marques-Bonet, T., Aksay, G., Antonacci, F., Hormozdiari, F., Kitzman, J. O., Baker, C., Malig, M., Mutlu, O., et al. (2009) · Nature Genetics · doi:10.1038/ng.437 · Cited by 748 · see citing works
Microfluidic Digital PCR Enables Multigene Analysis of Individual Environmental Bacteria
Ottesen, E. A., Hong, J. W., Quake, S. R., & Leadbetter, J. R. (2006) · Science · doi:10.1126/science.1131370 · Cited by 737 · see citing works
Diversity of Human Copy Number Variation and Multicopy Genes
Sudmant, P. H., Kitzman, J. O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., 1000 Genomes Project, et al. (2010) · Science · doi:10.1126/science.1197005 · Cited by 667 · see citing works
Quantitation of targets for PCR by use of limiting dilution.
Sykes, P. J., Neoh, S. H., Brisco, M. J., Hughes, E., Condon, J. C., & Morley, A. A. (1992) · PubMed · Cited by 621 · see citing works
Methods and strategies for analyzing copy number variation using DNA microarrays
Carter, N. P. (2007) · Nature Genetics · doi:10.1038/ng2028 · Cited by 510 · see citing works
BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions
Diehl, F., Li, M., He, Y., Kinzler, K. W., Vogelstein, B., & Dressman, D. C. (2006) · Nature Methods · doi:10.1038/nmeth898 · Cited by 496 · see citing works
Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR
Warren, L. A., Bryder, D., Weissman, I., & Quake, S. (2006) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0608512103 · Cited by 373 · see citing works
On-Chip, Real-Time, Single-Copy Polymerase Chain Reaction in Picoliter Droplets
Beer, N. R., Hindson, B. J., Wheeler, E. K., Hall, S. B., Rose, K. A., Kennedy, I. M., & Colston, B. W. (2007) · Analytical Chemistry · doi:10.1021/ac701809w · Cited by 358 · see citing works
Self-citationSensitive digital quantification of DNA methylation in clinical samples
Li, M., Chen, W.-D., Papadopoulos, N., Goodman, S. N., Bjerregaard, N. C., Laurberg, S., Levin, B., Juhl, H., Arber, N., Moinova, H., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1559 · Cited by 341 · see citing works
High-Throughput Quantitative Polymerase Chain Reaction in Picoliter Droplets
Kiss, M. M., Ortoleva-Donnelly, L., Beer, N. R., Warner, J. B., Bailey, C. G., Colston, B. W., Rothberg, J. M., Link, D. R., & Leamon, J. H. (2008) · Analytical Chemistry · doi:10.1021/ac801276c · Cited by 327 · see citing works
Self-citationDube, S., Qin, J., & Ramakrishnan, R. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002876 · Cited by 302 · see citing works
Self-citationAnalysis of the Size Distributions of Fetal and Maternal Cell-Free DNA by Paired-End Sequencing
Fan, H. C., Blumenfeld, Y. J., Chitkara, U., Hudgins, L., & Quake, S. R. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2010.144188 · Cited by 266 · see citing works
BEAMing up for detection and quantification of rare sequence variants
Li, M., Diehl, F., Dressman, D., Vogelstein, B., & Kinzler, K. W. (2006) · Nature Methods · doi:10.1038/nmeth850 · Cited by 261 · see citing works
The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis
Wright, C. F., & Burton, H. (2008) · Human Reproduction Update · doi:10.1093/humupd/dmn047 · Cited by 255 · see citing works
Nanoliter high throughput quantitative PCR
Morrison, T. B., Hurley, J., Garcia, J., Yoder, K., Katz, A., Roberts, D., Cho, J., Kanigan, T. S., Ilyin, S. E., Horowitz, D., et al. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl639 · Cited by 220 · see citing works
Weaver, S., Dube, S., Mir, A., Qin, J., Sun, G., Ramakrishnan, R., Jones, R. C., & Livak, K. J. (2010) · Methods · doi:10.1016/j.ymeth.2010.01.003 · Cited by 220 · see citing works
Self-citationOn-Chip Single-Copy Real-Time Reverse-Transcription PCR in Isolated Picoliter Droplets
Beer, N. R., Wheeler, E. K., Lee-Houghton, L., Watkins, N. N., Nasarabadi, S., Hebert, N. E., Leung, P., Arnold, D. W., Bailey, C. G., & Colston, B. W. (2008) · Analytical Chemistry · doi:10.1021/ac800048k · Cited by 209 · see citing works
Self-citationDetection of Aneuploidy with Digital Polymerase Chain Reaction
Fan, H. C., & Quake, S. R. (2007) · Analytical Chemistry · doi:10.1021/ac0709394 · Cited by 179 · see citing works
Kumar, S. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2005.062893 · Cited by 154 · see citing works
Detection of BRAF V600E Mutation in Colorectal Cancer
Benlloch, S., Payá, A., Alenda, C., Bessa, X., Andreu, M. G., Jover, R., Castells, A., Llor, X., Aranda, I., & Massutí, B. (2006) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2006.060070 · Cited by 144 · see citing works
Noninvasive Prenatal Detection of Trisomy 21 by an Epigenetic–Genetic Chromosome-Dosage Approach
Tong, Y. K., Jin, S., Chiu, R. W. K., et al. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2009.134114 · Cited by 129 · see citing works
Aldhous, M. C., Bakar, S. A., Prescott, N. J., Raquel, P., Soo, K., Mansfield, J. C., Mathew, C. G., Satsangi, J. J., & Armour, J. A. L. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq411 · Cited by 124 · see citing works
Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy
Fan, H. C., Blumenfeld, Y. J., El-Sayed, Y. Y., Chueh, J. T., & Quake, S. R. (2009) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2009.03.002 · Cited by 108 · see citing works
Studying copy number variations using a nanofluidic platform
Qin, J., Jones, R. C., & Ramakrishnan, R. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn518 · Cited by 102 · see citing works
Kauraniemi, P., Kuukasjärvi, T., Sauter, G., & Kallioniemi, A. H. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63556-0 · Cited by 91 · see citing works
Digital quantification of mutant DNA in cancer patients
Diehl, F., & Diaz, L. A. (2006) · Current Opinion in Oncology · doi:10.1097/cco.0b013e328011a8e7 · Cited by 53 · see citing works
Amplification and expression of genes from the 17q11∼q12 amplicon in breast cancer cells
Luoh, S. (2002) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(01)00657-4 · Cited by 48 · see citing works
McCaughan, F. M., & Dear, P. H. (2009) · The Journal of Pathology · doi:10.1002/path.2647 · Cited by 41 · see citing works
External Quality Assurance of HER2 FISH and ISH Testing
Bartlett, J. M. S., Ibrahim, M., Jasani, B., et al. (2008) · American Journal of Clinical Pathology · doi:10.1309/ajcpln78zqxemnma · Cited by 37 · see citing works
Hosono, N., Kubo, M., Tsuchiya, Y. N., Sato, H., Kitamoto, T., Saito, S., Ohnishi, Y., & Nakamura, Y. (2007) · Human Mutation · doi:10.1002/humu.20609 · Cited by 29 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Sykes P. J.; Neoh S. H.; Brisco M. J.; Hughes E.; Condon J.; Morley A. A. Biotechniques 1992, 13, 444–449. 1389177
- Sudmant P. H.; Kitzman J. O.; Antonacci F.; Alkan C.; Malig M.; Tsalenko A.; Sampas N.; Bruhn L.; Shendure J.; Eichler E. E. Science 2010, 330, 641–646.21030649
- Pathak A. K.; Bhutani M.; Kumar S.; Mohan A.; Guleria R. Clin. Chem. 2006, 52, 1833–1842. 16423903
Cited by
Sorted by citations
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353 · see citing works
Self-citationHighly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110 · see citing works
Gene Editing of <i>CCR5</i> in Autologous CD4 T Cells of Persons Infected with HIV
Tebas, P., Stein, D., Tang, W. W., Frank, I., Wang, S. Q., Lee, G., Spratt, S. K., Surosky, R. T., Giedlin, M. A., Nichol, G., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1300662 · Cited by 1,357 · see citing works
Self-citationPersonal omics profiling reveals dynamic molecular and medical phenotypes
Chen, R., Mias, G. I., Li-Pook-Than, J., Jiang, L., Lam, H. Y. K., Chen, R., Miriami, E., Karczewski, K. J., Hariharan, M., Dewey, F. E., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.009 · Cited by 1,291 · see citing works
Hata, A. N., Niederst, M. J., Archibald, H. L., Gomez-Caraballo, M., Siddiqui, F. M., Mulvey, H. E., Maruvka, Y. E., Ji, F., Bhang, H.-E. C., Krishnamurthy Radhakrishna, V., et al. (2016) · Nature Medicine · doi:10.1038/nm.4040 · Cited by 985 · see citing works
Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia
Wong, T. N., Ramsingh, G., Young, A. L., Miller, C. A., Touma, W., Welch, J. S., Lamprecht, T. L., Shen, D., Hundal, J., Fulton, R. S., et al. (2015) · Nature · doi:10.1038/nature13968 · Cited by 892 · see citing works
Huggett, J. F., Foy, C. A., Benes, V., Emslie, K., Garson, J. A., Haynes, R., Hellemans, J., Kubista, M., Mueller, R. D., Nolan, T., et al. (2013) · Clinical Chemistry · doi:10.1373/clinchem.2013.206375 · Cited by 859 · see citing works
Oxnard, G. R., Paweletz, C. P., Kuang, Y., Mach, S. L., O'Connell, A., Messineo, M. M., Luke, J. J., Butaney, M., Kirschmeier, P., Jackman, D. M., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2482 · Cited by 786 · see citing works
Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults
Young, A. L., Challen, G. A., Birmann, B. M., & Druley, T. E. (2016) · Nature Communications · doi:10.1038/ncomms12484 · Cited by 692 · see citing works
Taylor, S. C., Laperriere, G., & Germain, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-02217-x · Cited by 626 · see citing works
Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations
Merkle, F. T., Ghosh, S., Kamitaki, N., Mitchell, J., Avior, Y., Mello, C., Kashin, S., Mekhoubad, S., Ilic, D., Charlton, M., et al. (2017) · Nature · doi:10.1038/nature22312 · Cited by 506 · see citing works
Whale, A. S., Huggett, J. F., Cowen, S., Speirs, V., Shaw, J., Ellison, S., Foy, C. A., & Scott, D. J. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks203 · Cited by 453 · see citing works
Finkin, S., Yuan, D., Stein, I., Taniguchi, K., Weber, A., Unger, K., Browning, J. L., Goossens, N., Nakagawa, S., Gunasekaran, G., et al. (2015) · Nature Immunology · doi:10.1038/ni.3290 · Cited by 433 · see citing works
Resurrection of endogenous retroviruses during aging reinforces senescence
Liu, X., Liu, Z., Wu, Z., Ren, J., Fan, Y., Sun, L., Cao, G., Niu, Y., Zhang, B., Ji, Q., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.017 · Cited by 390 · see citing works
Self-citationDisentangling neural cell diversity using single-cell transcriptomics
Poulin, J.-F., Tasic, B., Hjerling-Leffler, J., Trimarchi, J. M., & Awatramani, R. (2016) · Nature Neuroscience · doi:10.1038/nn.4366 · Cited by 293 · see citing works
McConnell, M. J., Moran, J. V., Abyzov, A., Akbarian, S., Bae, T., Cortes-Ciriano, I., Erwin, J. A., Fasching, L., Flasch, D. A., Freed, D., et al. (2017) · Science · doi:10.1126/science.aal1641 · Cited by 262 · see citing works
<i>Fusobacterium nucleatum</i>and colorectal cancer: A review
Shang, F.-M., & Liu, H.-L. (2018) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v10.i3.71 · Cited by 258 · see citing works
Gimpel, A. L., Katsikis, G., Sha, S., Maloney, A. J., Hong, M. S., Nguyen, T. N. T., Wolfrum, J., Springs, S. L., Sinskey, A. J., Manalis, S. R., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.010 · Cited by 185 · see citing works
Chip in a lab: microfluidics for next generation life science research
Streets, A. M., & Huang, Y. (2013) · Biomicrofluidics · doi:10.1063/1.4789751 · Cited by 180 · see citing works
Lock, M., Alvira, M. R., Chen, S.-J., & Wilson, J. M. (2014) · Human Gene Therapy Methods · doi:10.1089/hgtb.2013.131 · Cited by 163 · see citing works
Taylor, S. C., Carbonneau, J., Shelton, D. N., & Boivin, G. (2015) · Journal of Virological Methods · doi:10.1016/j.jviromet.2015.08.014 · Cited by 142 · see citing works
O'Hara, R., Tedone, E., Ludlow, A., Huang, E., Arosio, B., Mari, D., & Shay, J. W. (2019) · Genome Research · doi:10.1101/gr.250480.119 · Cited by 121 · see citing works
Hereditary alpha-tryptasemia: UK prevalence and variability in disease expression
Robey, R. C., Wilcock, A., Bonin, H., Beaman, G., Myers, B., Grattan, C., Briggs, T. A., & Arkwright, P. D. (2020) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2020.05.057 · Cited by 119 · see citing works
Digital PCR: A Sensitive and Precise Method for KIT D816V Quantification in Mastocytosis
Greiner, G., Gurbisz, M., Ratzinger, F., Witzeneder, N., Simonitsch-Klupp, I., Mitterbauer-Hohendanner, G., Mayerhofer, M., Müllauer, L., Sperr, W. R., Valent, P., et al. (2018) · Clinical Chemistry · doi:10.1373/clinchem.2017.277897 · Cited by 83 · see citing works
Taylor, S. D., Ericson, N. G., Burton, J. N., Prolla, T. A., Silber, J. R., Shendure, J., & Bielas, J. H. (2014) · Aging Cell · doi:10.1111/acel.12146 · Cited by 67 · see citing works
Furuta-Hanawa, B., Yamaguchi, T., & Uchida, E. (2019) · Human Gene Therapy Methods · doi:10.1089/hgtb.2019.031 · Cited by 60 · see citing works
LC3B is indispensable for selective autophagy of p62 but not basal autophagy.
Maruyama, Y., Sou, Y.-S., Kageyama, S., Takahashi, T., Ueno, T., Tanaka, K., Komatsu, M., & Ichimura, Y. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.02.093 · Cited by 56 · see citing works
Hughesman, C. B., Lu, X. J. D., Liu, K. Y. P., Zhu, Y., Poh, C. F., & Haynes, C. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161274 · Cited by 46 · see citing works
Analysis of Extracellular RNA by Digital PCR
Takahashi, K., Yan, I. K., Kim, C., Kim, J., & Patel, T. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00129 · Cited by 51 · see citing works
“Digital polymerase chain reaction (dPCR) provides an alternative approach for the detection of gene expression in the setting where the amount of target RNA is low and approaching the limits of sensitivity of qPCR (10).”
BackgroundBias and Imprecision in Analysis of Real-Time Quantitative Polymerase Chain Reaction Data
Tellinghuisen, J., & Spiess, A.-N. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02057 · Cited by 35 · see citing works
Blasi, T., Buettner, F., Strasser, M. K., Marr, C., & Theis, F. J. (2017) · Physical Biology · doi:10.1088/1478-3975/aa609a · Cited by 18 · see citing works
Limits of the Classical Concept of Concentration
Maioli, M., Varadi, G., Kurdi, R., Caglioti, L., & Pályi, G. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b02904 · Cited by 13 · see citing works
- Authors
- Hindson, B. J., Ness, K. D., Masquelier, D. A., Belgrader, P., Heredia, N. J., Makarewicz, A. J., Bright, I. J., Lucero, M. Y., Hiddessen, A. L., Legler, T. C., Kitano, T. K., Hodel, M. R., Petersen, J. F., Wyatt, P. W., Steenblock, E. R., Shah, P. H., Bousse, L. J., Troup, C. B., Mellen, J. C., Wittmann, D. K., Erndt, N. G., Cauley, T. H., Koehler, R. T., So, A. P., Dube, S., Rose, K. A., Montesclaros, L., Wang, S., Stumbo, D. P., Hodges, S. P., Romine, S., Milanovich, F. P., White, H. E., Regan, J. F., Karlin-Neumann, G. A., Hindson, C. M., Saxonov, S., & Colston, B. W.
- Affiliations
- Bio-Rad (United States) (US)
- Bio-Rad Laboratories, Inc., 7068 Koll Center Parkway, Pleasanton, California 94566, United States
- Salisbury District Hospital (GB)
- Corresponding author
- Hindson, Benjamin J.
- ORCID
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-10-28
- Volume
- 83
- Issue
- 22
- Pages
- 8604-8610
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- PMC
- PMC3216358
- OpenAlex
- W2064543601
- Cited by
- 2,792
- References
- 37
- Citations by year
- 2026: 218 · 2025: 204 · 2024: 196 · 2023: 213 · 2022: 204 · 2021: 263 · 2020: 257 · 2019: 234 · 2018: 221 · 2017: 191 · 2016: 190 · 2015: 153 · 2014: 130 · 2013: 74 · 2012: 35
- FWCI
- 31.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Analytical Chemistry (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Physical Sciences › Engineering › Biomedical Engineering › Innovative Microfluidic and Catalytic Techniques Innovation
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- droplet digital PCR, DNA copy number, germline copy number variation, cell-free DNA, cell-free plasma, fetal DNA, TaqMan real-time PCR, molecular diagnosis
- MeSH terms
- DNA, Humans, Polymerase Chain Reaction, Gene Dosage, High-Throughput Nucleotide Sequencing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
