ES2595373T3 - Prueba genética no invasiva mediante análisis digital - Google Patents

Prueba genética no invasiva mediante análisis digital Download PDF

Info

Publication number
ES2595373T3
ES2595373T3 ES11175845.4T ES11175845T ES2595373T3 ES 2595373 T3 ES2595373 T3 ES 2595373T3 ES 11175845 T ES11175845 T ES 11175845T ES 2595373 T3 ES2595373 T3 ES 2595373T3
Authority
ES
Spain
Prior art keywords
maternal
target sequences
genetic material
fetal
discrete samples
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES11175845.4T
Other languages
English (en)
Inventor
Stephen Quake
Hei-Mun Christina Fan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Leland Stanford Junior University
Original Assignee
Leland Stanford Junior University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38345760&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ES2595373(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Leland Stanford Junior University filed Critical Leland Stanford Junior University
Application granted granted Critical
Publication of ES2595373T3 publication Critical patent/ES2595373T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6809—Methods for determination or identification of nucleic acids involving differential detection
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6851—Quantitative amplification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6858—Allele-specific amplification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6881—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Abstract

Un método para detectar una anormalidad genética que implica una diferencia cuantitativa entre secuencias genéticas maternas y fetales por la detección diferencial de las secuencias diana en una mezcla de material genético materno y fetal, que comprende las etapas de: a)la distribución del material genético en muestras discretas, conteniendo cada muestra en promedio no más de una secuencia diana por muestra, en el que las muestras discretas están en muestras de reacción donde se pueden analizar las secuencias diana; b)la medición de la presencia de diferentes secuencias diana en las muestras discretas, en la que la medición comprende la secuenciación directa del material genético o secuenciación de derivados amplificados de las secuencias diana en clones o amplicones del material genético; y, c) el análisis de un número de las muestras discretas, donde el número de muestras discretas analizadas y los resultados de las muestras discretas proporcionan datos suficientes para obtener resultados que distinguen dichas secuencias diana diferentes. donde una de las diferentes secuencias diana es diploide en el material genético materno y aneuploides en el material genético fetal y otra de las diferentes secuencias diana es diploide, tanto en el material genético materno como en el fetal, detectando de ese modo una anomalía genética que implica una diferencia cuantitativa entre secuencias genéticas maternas y fetales.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
puede ser excluidao. Otra etapa de enriquecimiento puede ser para el tratamiento de la muestra de sangre con formaldehído, como se describe en Dhallan et al.. " Methods to Increase the Percentage of Free Fetal ADN Recovered From the Maternal Circulation," J. Am Medicina. Soc. 291 (9):1114-1119 (Marzo 2004).
2.
La distribución de las moléculas individuales de ADN de esta muestra a una serie de muestras de reacción discretas, donde se selecciona el número de muestras de reacción para dar un resultado estadísticamentesignificativo para elnúmero de copias de una diana en lasmoléculasde ADN.Además,la muestra de reacción se limita a un pequeño volumen para que las moléculas de reacción en estrecha aproximación. La cantidad de molécula de ADN por muestra de reacción es preferiblemente del orden de una copia del cromosoma de interés equivalente pormuestra de reacción.
3.
La detección de la presencia de la diana en el ADN en un gran número de muestras de reacción, preferiblemente con una técnica específica de secuencia como la secuenciación de lectura corta altamente multiplexada o una reacción de PCR en el que el producto de PCR se marca para producir una lectura cuantitativamente conveniente. La etapa de detección se denomina aquí "PCR digital" y puede ser llevada a cabo por una variedad de métodos, tales como (a) por PCR en muestras diluidas en pocillos individuales de una placa de microtitulación; (b) PCR en muestras diluidas en emulsiones que contienen cebadores inmovilizados a microesferas; o (c) PCR en muestras atrapadas en una cámara de microfluidos; y
4.
El análisis cuantitativo de la detección de las secuencias diana maternas y fetales. En algunos casos, esto puede incluir dianas a diferentes regiones, tales como sondas para un diana en un cromosoma sospechoso de estar presente en un número de copia anormal (trisonomía) en comparación con un cromosoma diploide normal, que se utiliza como control.
II.
Descripción de los Pasos
A.
Preparación de tejidos
[0038] El presente procedimiento se refiere a pruebas no invasivas. El material de partida preferido es sangre venosa periférica materna. Con el fin de obtener suficiente ADN para la prueba, se prefiere que se extraiga 10 a 20 mldesangre,afindeobteneralrededorde almenos10.000 equivalentes de genoma de ADN total.Este tamaño de la muestra se basa en una estimación de estar presente el ADN fetal como más o menos 25 equivalentes de genoma/ml de plasmamaterno en elembarazo temprano,yunaconcentración de ADN fetal de aproximadamente el 3,4% del ADN total en plasma. Sin embargo, menos sangre puede extraerse para una pantalla genética donde se requiere menos significación estadística, o la muestra de ADN se enriquece para el ADN fetal.
[0039] Cabe señalar que, aunque la presente descripción se refiere a ADN, ARN fetal encontrado en la sangre materna se puede analizar también. Como se describe en Ng et al.., "mRNA of placental origin is readily detectable in maternal plasma," Proc. Nat. Acad. Sci. 100 (8):4.748-4.753 (2003), HPL (lactógeno placentario humano) y hCG (gonadotropina coriónica humana) transcritos de ARNm eran detectables en el plasma materno, tal comose analizó mediante los ensayos en tiempo real RT-PCR respectivos. En el presente método, el ARNm que codifican genes expresados en la placenta y el presente en el cromosoma de arco de interés utilizado. Por ejemplo, DSCR4 (región crítica 4 de Síndrome de Down) se encuentra en el cromosoma 21 y se expresa principalmente en la placenta. Su secuencia de ARNm se puede encontrar en GenBank NM_005867. En este caso, se prefiere utilizar RNasa H menos (RNasa H) transcriptasas inversas (RT) para preparar cADN para la detección. RNasa H-RTs están disponibles de varios fabricantes, con SuperScriptTM II (Invitrogen), siendo el más ampliamente utilizado. La transcriptasa inversa PCR se puede usar como se describe a continuación para el ADN cromosómico.
i. Enriquecimiento de ADN o ARN a partir de plasma
[0040] La sangre materna se puede procesar para enriquecer la concentración de ADN fetal en el ADN total, como se describe en Li et al.., supra. Brevemente, el ADN circulatorio se extrae de plasma materno 5-a 10 ml utilizando la tecnología de la columna comercial (Roche High. Pure Template ADN Purification Kit; Roche, Basel, Suiza) en combinación con una bomba de vacío. Después de la extracción, el ADN se separa por electroforesis en gel de agarosa (1%) de electroforesis (Invitrogen, Basilea, Suiza), y la fracción de gel que contiene ADN circulatorio con un tamaño de aproximadamente 300 pb se escindió cuidadosamente. El ADN se extrae de esta porción de gel utilizando un kit de extracción (QIAEX II Gel Extraction Kit; Qiagen, Basilea, Suiza) y se eluyó en un volumen final de 40 µl de ácido trishidroclórico 10-mM estéril, pH 8,0 (Roche).
[0041] ADN puede ser concentrado por métodos conocidos, incluyendo centrifugación y diversos inhibidores de la enzima.El ADN se unea una membrana selectiva (porejemplo, sílice)para separarlo de contaminantes.El ADN se enriquece preferiblemente para los fragmentos que circulan en el plasma, que son menos de 1000 pares de bases de longitud, generalmente de menos de 300 pb. Esta selección de tamaño se realiza en unmedio de separación de tamaño de ADN, tal como un gel electroforético o material de cromatografía. Tal material se describe en Huber et al.., " High-resolution liquid chromatography of ADN fragments on non-porous poly(styrene-divinylbenzene) particles," Nucleic Acids Res. 1993 de marzo de 11; 21 (5):1061-1066, cromatografía de filtración en gel, gel TSK, tal como se
8
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
[0098] La PCR digital permite la detección de aneuploidía meramente contando las transcripciones, como se ilustra mediante elsiguiente cálculo. Supongamos que el ADN fetal está presente en lasangre materna a un nivel fracción de ε, yque estamos tratando de descubriruna aneuploid ía de orden relativa a euploidía e (en el ejemplo, en relación a la detección del Síndrome de Down en los seres humanos, e=2 es euploidía y el Síndrome de Down trisomía α=3). Si cromosoma A es euploides y representa un control interno, y el cromosoma B es aneuploides y es el diana a medirse, entonces se puede amplificar segmentos representativos de ambos cromosomas mediante PCR digital. En la comparación de los amplicones de cada tipo, uno espera encontrar que por cada e amplicones de cromosoma A hay e(1-ε)+αε amplicones de cromosoma B. En el caso de una trisom ía y ε=3%, entonces para cada 2 amplicones del cromosoma A uno espera 2,03 amplicones de cromosomas B. Mientras que esta diferencia es pequeña, que se pueden medir. Por ejemplo, si uno amplifica una muestra de 1.000 equivalentes celulares, a continuación, uno espera 2.000 amplicones de cromosoma A y 2030 de cromosoma B. La diferencia de 30 amplicones es en principio detectable.
[0099] La confianza estadística requerida para resolver la diferencia en las proporciones se puede estimar de la siguiente manera. Ahí es una variación estadística aleatoria asociada con el tamaño de la muestra inicial, que va aproximadamente como la raíz cuadrada del número de muestras tomadas. De hecho, es a menudo difícil de comenzar con precisión con un número fijo de células equivalentes, y en el ejemplo anterior se espera un error estadístico de orden 32 amplicones (raíz cuadrada 32 (1000)) para la mayoría de las técnicas de preparación de muestras. Este es el mismo tamaño que la señal que estamos tratando de detectar y por lo tanto en la práctica se requiere más de 1.000 equivalentes celulares para la detección robusta. Precismante cuántos se requiere depende de la certeza estadística que se requiere. Si a uno le gustaría un resultado que es significativo para desviaciones estándar k en consecuancia
imagen15
[0100] Utilizando los valores del ejemplo anterior, si se requiere desviaciones estándar k=3, entonces el número de amplicones N debe ser de al menos 10.000 para la detección de Síndrome de Down. Sin embargo, como se discutió anteriormente, el número de secuencias diana necesarios para la confianza estadística se puede reducir mediante el uso de secuencias de control, y, además, la muestra puede ser enriquecida para el ADN fetal.
III. Aplicaciones específicas
[0101] La presente invención está particularmente adaptada para detectar anomalías genéticas que involucran diferencias cuantitativas entre las secuencias genéticas maternas y fetales. Estas anomalías genéticas incluyen mutaciones que pueden ser heterocigotos y homocigotos entre el ADN materno y fetal, y para aneuploidías. Por ejemplo, una copia que falta de cromosoma X (monosomía X) resulta en el Síndrome de Turner, mientras que una copia adicional del cromosoma 21 resulta en el Síndrome de Down. Otras enfermedades, como el síndrome de Edward y síndrome de Patau son causadas por una copia adicional del cromosoma 18 y el cromosoma 13, respectivamente. El presente método puede ser utilizado para la detección de una translocación. Además, la amplificación, transversión, inversión, aneuploidía, poliploidía, monosomía, trisomía, trisomía 21, trisomía 13, trisomía 14, trisomía 15, trisomía 16, trisomía 18, trisomía 22, triploidía, tetraploidia, y anomalías de cromosomas sexuales incluyendo, pero no limitado a XO, XXY, XYY, y XXX.
[0102] Otros cebadores específicos de cromosoma se describen en lasolicitud de patente de EE.UU. 20050164241 a Hahn, Sinuhé, et al., publicada el 28 de julio de 2005, titulada "Non-invasive detection of fetal genetic traits," aquí referenciada para la descripción de los métodos de preparación de muestras y ciertos cebadores de PCR, descritos como sigue:
Los cebadores para los genes se preparan sobre la base de secuencias de nucleótidos obtenidas a partir de bases de datos como GenBank, EMBL y similares. Los nombres de los cebadores polimórficos y las secuencias de los cebadores para los genes se muestran para los cromosomas respectivos en los siguientes ejemplos (#2, el Ejemplo 1; #4, Ejemplo 6, #14, el Ejemplo 9; #22, Ejemplo 2). Los siguientes marcadores genéticos polimórficos y fabricantes (pares de cebadores STS polimórficos: D2S207, D2S177, D2S156 y D2S159, BIOS Laboratories, Inc.) se utilizan para identificar el cromosoma #2.
[0103] Haymás de 1.000 conjuntos de cebadores de cromosoma 21 de PCR específicos que figuran en el sitio web del NIH UniSTS, que pueden estar situados en http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=unists y se encuentran con la frase de búsqueda "human[organism] AND 21[chr]". UniSTS es una base de datos completa de sitios de secuencia etiquetada (STS) derivados de mapas basados en STS y otros experimentos. STS están definidasporparesde cebadoresde PCR yseasocianconinformación adicional,como posición genómica,genes y secuencias. Del mismo modo, las secuencias de cebadores para otros cromosomas humanos se pueden encontrar modificando adecuadamente la consulta de búsqueda.
17
imagen16
imagen17
imagen18
imagen19
imagen20

Claims (1)

  1. imagen1
ES11175845.4T 2006-02-02 2007-02-02 Prueba genética no invasiva mediante análisis digital Active ES2595373T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US76442006P 2006-02-02 2006-02-02
US764420P 2006-02-02

Publications (1)

Publication Number Publication Date
ES2595373T3 true ES2595373T3 (es) 2016-12-29

Family

ID=38345760

Family Applications (4)

Application Number Title Priority Date Filing Date
ES11175845.4T Active ES2595373T3 (es) 2006-02-02 2007-02-02 Prueba genética no invasiva mediante análisis digital
ES15195673T Active ES2739484T3 (es) 2006-02-02 2007-02-02 Prueba genética fetal no invasiva mediante análisis digital
ES15195663T Active ES2739483T3 (es) 2006-02-02 2007-02-02 Detección genética fetal no invasiva mediante análisis digital
ES07763674T Active ES2429408T5 (es) 2006-02-02 2007-02-02 Examen genético fetal no invasivo mediante análisis digital

Family Applications After (3)

Application Number Title Priority Date Filing Date
ES15195673T Active ES2739484T3 (es) 2006-02-02 2007-02-02 Prueba genética fetal no invasiva mediante análisis digital
ES15195663T Active ES2739483T3 (es) 2006-02-02 2007-02-02 Detección genética fetal no invasiva mediante análisis digital
ES07763674T Active ES2429408T5 (es) 2006-02-02 2007-02-02 Examen genético fetal no invasivo mediante análisis digital

Country Status (13)

Country Link
US (11) US7888017B2 (es)
EP (6) EP3591068A1 (es)
CY (2) CY1118095T1 (es)
DK (3) DK1981995T4 (es)
ES (4) ES2595373T3 (es)
HK (1) HK1119206A1 (es)
HU (2) HUE045358T2 (es)
LT (2) LT3002338T (es)
PL (3) PL2385143T3 (es)
PT (2) PT2385143T (es)
SI (3) SI2385143T1 (es)
TR (1) TR201910868T4 (es)
WO (1) WO2007092473A2 (es)

Families Citing this family (359)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2445204C (en) 2002-10-16 2014-08-12 Streck Laboratories, Inc. Method and device for collecting and preserving cells for analysis
US20100022414A1 (en) 2008-07-18 2010-01-28 Raindance Technologies, Inc. Droplet Libraries
GB0307428D0 (en) 2003-03-31 2003-05-07 Medical Res Council Compartmentalised combinatorial chemistry
US20060078893A1 (en) 2004-10-12 2006-04-13 Medical Research Council Compartmentalised combinatorial chemistry by microfluidic control
EP1720636A4 (en) 2004-02-02 2012-06-20 Univ British Columbia SCODAPHORESIS, METHODS AND APPARATUS FOR DISPLACING AND CONCENTRATING PARTICLES
US8518228B2 (en) 2011-05-20 2013-08-27 The University Of British Columbia Systems and methods for enhanced SCODA
US10337054B2 (en) 2004-02-02 2019-07-02 Quantum-Si Incorporated Enrichment of nucleic acid targets
US8529744B2 (en) 2004-02-02 2013-09-10 Boreal Genomics Corp. Enrichment of nucleic acid targets
US20050221339A1 (en) 2004-03-31 2005-10-06 Medical Research Council Harvard University Compartmentalised screening by microfluidic control
US8024128B2 (en) * 2004-09-07 2011-09-20 Gene Security Network, Inc. System and method for improving clinical decisions by aggregating, validating and analysing genetic and phenotypic data
US7968287B2 (en) 2004-10-08 2011-06-28 Medical Research Council Harvard University In vitro evolution in microfluidic systems
US20060223178A1 (en) * 2005-04-05 2006-10-05 Tom Barber Devices and methods for magnetic enrichment of cells and other particles
US20070196820A1 (en) 2005-04-05 2007-08-23 Ravi Kapur Devices and methods for enrichment and alteration of cells and other particles
US20070026418A1 (en) * 2005-07-29 2007-02-01 Martin Fuchs Devices and methods for enrichment and alteration of circulating tumor cells and other particles
WO2007044091A2 (en) * 2005-06-02 2007-04-19 Fluidigm Corporation Analysis using microfluidic partitioning devices
US20070027636A1 (en) * 2005-07-29 2007-02-01 Matthew Rabinowitz System and method for using genetic, phentoypic and clinical data to make predictions for clinical or lifestyle decisions
US10083273B2 (en) 2005-07-29 2018-09-25 Natera, Inc. System and method for cleaning noisy genetic data and determining chromosome copy number
US8532930B2 (en) * 2005-11-26 2013-09-10 Natera, Inc. Method for determining the number of copies of a chromosome in the genome of a target individual using genetic data from genetically related individuals
US8921102B2 (en) 2005-07-29 2014-12-30 Gpb Scientific, Llc Devices and methods for enrichment and alteration of circulating tumor cells and other particles
US11111544B2 (en) 2005-07-29 2021-09-07 Natera, Inc. System and method for cleaning noisy genetic data and determining chromosome copy number
US20070178501A1 (en) * 2005-12-06 2007-08-02 Matthew Rabinowitz System and method for integrating and validating genotypic, phenotypic and medical information into a database according to a standardized ontology
US8515679B2 (en) * 2005-12-06 2013-08-20 Natera, Inc. System and method for cleaning noisy genetic data and determining chromosome copy number
US9424392B2 (en) 2005-11-26 2016-08-23 Natera, Inc. System and method for cleaning noisy genetic data from target individuals using genetic data from genetically related individuals
US10081839B2 (en) 2005-07-29 2018-09-25 Natera, Inc System and method for cleaning noisy genetic data and determining chromosome copy number
US11111543B2 (en) 2005-07-29 2021-09-07 Natera, Inc. System and method for cleaning noisy genetic data and determining chromosome copy number
WO2007044974A2 (en) * 2005-10-12 2007-04-19 The Research Foundation Of State University Of New York Absolute pcr quantification
WO2007081386A2 (en) 2006-01-11 2007-07-19 Raindance Technologies, Inc. Microfluidic devices and methods of use
ES2595373T3 (es) * 2006-02-02 2016-12-29 The Board Of Trustees Of The Leland Stanford Junior University Prueba genética no invasiva mediante análisis digital
AU2007223102A1 (en) * 2006-03-06 2007-09-13 The Trustees Of Columbia University In The City Of New York Specific amplification of fetal DNA sequences from a mixed, fetal-maternal source
DE602007003331D1 (de) * 2006-04-12 2009-12-31 Medical Res Council Verfahren zur bestimmung der kopienummer
JP2010506136A (ja) 2006-05-11 2010-02-25 レインダンス テクノロジーズ， インコーポレイテッド 微小流体デバイス
US9562837B2 (en) 2006-05-11 2017-02-07 Raindance Technologies, Inc. Systems for handling microfludic droplets
EP2602321B1 (en) 2006-05-31 2017-08-23 Sequenom, Inc. Methods and compositions for the extraction and amplification of nucleic acid from a sample
US20080050739A1 (en) 2006-06-14 2008-02-28 Roland Stoughton Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats
WO2007147074A2 (en) * 2006-06-14 2007-12-21 Living Microsystems, Inc. Use of highly parallel snp genotyping for fetal diagnosis
US8137912B2 (en) 2006-06-14 2012-03-20 The General Hospital Corporation Methods for the diagnosis of fetal abnormalities
EP2589668A1 (en) * 2006-06-14 2013-05-08 Verinata Health, Inc Rare cell analysis using sample splitting and DNA tags
WO2008111990A1 (en) * 2006-06-14 2008-09-18 Cellpoint Diagnostics, Inc. Rare cell analysis using sample splitting and dna tags
EP3536396B1 (en) 2006-08-07 2022-03-30 The President and Fellows of Harvard College Fluorocarbon emulsion stabilizing surfactants
US7902345B2 (en) 2006-12-05 2011-03-08 Sequenom, Inc. Detection and quantification of biomolecules using mass spectrometry
WO2008097559A2 (en) 2007-02-06 2008-08-14 Brandeis University Manipulation of fluids and reactions in microfluidic systems
US8592221B2 (en) 2007-04-19 2013-11-26 Brandeis University Manipulation of fluids, fluid components and reactions in microfluidic systems
AU2013200581B2 (en) * 2007-07-23 2014-06-05 The Chinese University Of Hong Kong Diagnosing cancer using genomic sequencing
EA201201551A1 (ru) * 2007-07-23 2013-08-30 Те Чайниз Юниверсити Ов Гонконг Способ диагностики рака с использованием геномного секвенирования
AU2013202132C1 (en) * 2007-07-23 2019-07-04 The Chinese University Of Hong Kong Determining a nucleic acid sequence imbalance using multiple markers
US20100112590A1 (en) * 2007-07-23 2010-05-06 The Chinese University Of Hong Kong Diagnosing Fetal Chromosomal Aneuploidy Using Genomic Sequencing With Enrichment
AU2013203077B2 (en) * 2007-07-23 2014-05-08 The Chinese University Of Hong Kong Diagnosing fetal chromosomal aneuploidy using genomic sequencing
US20090053719A1 (en) * 2007-08-03 2009-02-26 The Chinese University Of Hong Kong Analysis of nucleic acids by digital pcr
EP2195452B1 (en) 2007-08-29 2012-03-14 Sequenom, Inc. Methods and compositions for universal size-specific polymerase chain reaction
EA018555B1 (ru) 2007-09-07 2013-08-30 Флуидигм Корпорейшн Определение вариаций количества копий, способы и системы
US8852864B2 (en) 2008-01-17 2014-10-07 Sequenom Inc. Methods and compositions for the analysis of nucleic acids
US8475641B2 (en) 2008-02-01 2013-07-02 The University Of British Columbia Methods and apparatus for particle introduction and recovery
US8173080B2 (en) 2008-02-14 2012-05-08 Illumina, Inc. Flow cells and manifolds having an electroosmotic pump
WO2009105531A1 (en) * 2008-02-19 2009-08-27 Gene Security Network, Inc. Methods for cell genotyping
WO2009114543A2 (en) 2008-03-11 2009-09-17 Sequenom, Inc. Nucleic acid-based tests for prenatal gender determination
DE102008019132A1 (de) * 2008-04-16 2009-10-22 Olympus Life Science Research Europa Gmbh Verfahren zur quantitativen Bestimmung der Kopienzahl einer vorbestimmten Sequenz in einer Probe
WO2009146335A1 (en) * 2008-05-27 2009-12-03 Gene Security Network, Inc. Methods for embryo characterization and comparison
WO2010012002A1 (en) * 2008-07-25 2010-01-28 Saryna Medical Corporation Methods and systems for genetic analysis of fetal nucleated red blood cells
CN104732118B (zh) 2008-08-04 2017-08-22 纳特拉公司 等位基因调用和倍性调用的方法
CN102138317B (zh) * 2008-08-04 2015-08-26 Nec欧洲有限公司 用于在移动通信系统中促进通信的方法和移动通信系统
EP4008795A1 (en) * 2008-08-12 2022-06-08 Stokes Bio Limited Methods for digital pcr
WO2010021936A1 (en) * 2008-08-16 2010-02-25 The Board Of Trustees Of The Leland Stanford Junior University Digital pcr calibration for high throughput sequencing
US8962247B2 (en) 2008-09-16 2015-02-24 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses
JP5727375B2 (ja) 2008-09-16 2015-06-03 セクエノム， インコーポレイテッド 非侵襲性の出生前診断のために有用な、母体サンプル由来の胎児核酸のメチル化に基づく濃縮のためのプロセスおよび組成物
US8476013B2 (en) 2008-09-16 2013-07-02 Sequenom, Inc. Processes and compositions for methylation-based acid enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
EP3378951B1 (en) 2008-09-20 2020-05-13 The Board of Trustees of the Leland Stanford Junior University Noninvasive diagnosis of aneuploidy by sequencing
AU2015202167B2 (en) * 2008-09-20 2017-12-21 The Board Of Trustees Of The Leland Stanford Junior University Noninvasive diagnosis of fetal aneuploidy by sequencing
US20110159499A1 (en) * 2009-11-25 2011-06-30 Quantalife, Inc. Methods and compositions for detecting genetic material
US8709762B2 (en) 2010-03-02 2014-04-29 Bio-Rad Laboratories, Inc. System for hot-start amplification via a multiple emulsion
US11130128B2 (en) 2008-09-23 2021-09-28 Bio-Rad Laboratories, Inc. Detection method for a target nucleic acid
US9492797B2 (en) 2008-09-23 2016-11-15 Bio-Rad Laboratories, Inc. System for detection of spaced droplets
US9399215B2 (en) 2012-04-13 2016-07-26 Bio-Rad Laboratories, Inc. Sample holder with a well having a wicking promoter
US10512910B2 (en) 2008-09-23 2019-12-24 Bio-Rad Laboratories, Inc. Droplet-based analysis method
US8663920B2 (en) 2011-07-29 2014-03-04 Bio-Rad Laboratories, Inc. Library characterization by digital assay
US9132394B2 (en) 2008-09-23 2015-09-15 Bio-Rad Laboratories, Inc. System for detection of spaced droplets
US9417190B2 (en) 2008-09-23 2016-08-16 Bio-Rad Laboratories, Inc. Calibrations and controls for droplet-based assays
US9156010B2 (en) 2008-09-23 2015-10-13 Bio-Rad Laboratories, Inc. Droplet-based assay system
US8951939B2 (en) 2011-07-12 2015-02-10 Bio-Rad Laboratories, Inc. Digital assays with multiplexed detection of two or more targets in the same optical channel
US8633015B2 (en) 2008-09-23 2014-01-21 Bio-Rad Laboratories, Inc. Flow-based thermocycling system with thermoelectric cooler
US20120252015A1 (en) * 2011-02-18 2012-10-04 Bio-Rad Laboratories Methods and compositions for detecting genetic material
US9764322B2 (en) 2008-09-23 2017-09-19 Bio-Rad Laboratories, Inc. System for generating droplets with pressure monitoring
US20100112588A1 (en) * 2008-11-04 2010-05-06 Caerus Molecular Diagnostics, Inc. Methods for sanger sequencing using particle associated clonal amplicons and highly parallel electrophoretic size-based separation
WO2010062965A2 (en) 2008-11-26 2010-06-03 Illumina Corporation Electroosmotic pump with improved gas management
SG172345A1 (en) * 2008-12-22 2011-07-28 Celula Inc Methods and genotyping panels for detecting alleles, genomes, and transcriptomes
US20100167271A1 (en) * 2008-12-30 2010-07-01 Streck, Inc. Method for screening blood using a preservative that may be in a substantially solid state form
US11634747B2 (en) 2009-01-21 2023-04-25 Streck Llc Preservation of fetal nucleic acids in maternal plasma
DE202010018561U1 (de) 2009-01-21 2017-08-28 Streck Inc. Blutsammelröhrchen
US20100298453A1 (en) * 2009-01-26 2010-11-25 Invista North America S.A R.L. Board stock foam having biobased content
EP3290530B1 (en) 2009-02-18 2020-09-02 Streck Inc. Preservation of cell-free nucleic acids
US9464319B2 (en) 2009-03-24 2016-10-11 California Institute Of Technology Multivolume devices, kits and related methods for quantification of nucleic acids and other analytes
US9447461B2 (en) 2009-03-24 2016-09-20 California Institute Of Technology Analysis devices, kits, and related methods for digital quantification of nucleic acids and other analytes
CA2756463C (en) 2009-03-24 2019-01-22 University Of Chicago Slip chip device and methods
US10196700B2 (en) 2009-03-24 2019-02-05 University Of Chicago Multivolume devices, kits and related methods for quantification and detection of nucleic acids and other analytes
EP3964586A1 (en) 2009-04-03 2022-03-09 Sequenom, Inc. Nucleic acid preparation compositions and methods
US8877028B2 (en) 2009-04-21 2014-11-04 The University Of British Columbia System and methods for detection of particles
WO2010123626A1 (en) 2009-04-24 2010-10-28 University Of Southern California Cd133 polymorphisms and expression predict clinical outcome in patients with cancer
US20110027771A1 (en) * 2009-07-31 2011-02-03 Artemis Health, Inc. Methods and compositions for cell stabilization
JP6155418B2 (ja) 2009-09-02 2017-07-05 バイオ−ラッド・ラボラトリーズ・インコーポレーテッド 多重エマルジョンの合体による、流体を混合するためのシステム
CN102597266A (zh) 2009-09-30 2012-07-18 纳特拉公司 无创性产前倍性调用的方法
WO2011053790A2 (en) * 2009-10-30 2011-05-05 Fluidigm Corporation Assay of closely linked targets in fetal diagnosis and coincidence detection assay for genetic analysis
DK3783110T3 (da) 2009-11-05 2023-02-06 Univ Hong Kong Chinese Føtal genomisk analyse fra en maternel biologisk prøve
EP4212630A1 (en) 2009-11-06 2023-07-19 The Chinese University of Hong Kong Size-based genomic analysis
EP3719140A1 (en) 2009-11-06 2020-10-07 The Board Of Trustees Of The Leland Stanford Junior University Non-invasive diagnosis of graft rejection in organ transplant patients
EP3103883A1 (en) * 2009-11-09 2016-12-14 Streck, Inc. Stabilization of rna in and extracting from intact cells within a blood sample
US20120288861A1 (en) 2009-12-21 2012-11-15 Heinz-Josef Lenz Germline polymorphisms in the sparc gene associated with clinical outcome in gastric cancer
ES2577017T3 (es) 2009-12-22 2016-07-12 Sequenom, Inc. Procedimientos y kits para identificar la aneuploidia
US8574842B2 (en) * 2009-12-22 2013-11-05 The Board Of Trustees Of The Leland Stanford Junior University Direct molecular diagnosis of fetal aneuploidy
US10837883B2 (en) 2009-12-23 2020-11-17 Bio-Rad Laboratories, Inc. Microfluidic systems and methods for reducing the exchange of molecules between droplets
WO2011085334A1 (en) 2010-01-11 2011-07-14 University Of Southern California Cd44 polymorphisms predict clinical outcome in patients with gastric cancer
US10388403B2 (en) 2010-01-19 2019-08-20 Verinata Health, Inc. Analyzing copy number variation in the detection of cancer
ES2704701T3 (es) 2010-01-19 2019-03-19 Verinata Health Inc Nuevo protocolo de preparación de bibliotecas de secuenciación
EP2513341B1 (en) 2010-01-19 2017-04-12 Verinata Health, Inc Identification of polymorphic sequences in mixtures of genomic dna by whole genome sequencing
US20120100548A1 (en) 2010-10-26 2012-04-26 Verinata Health, Inc. Method for determining copy number variations
US9260745B2 (en) 2010-01-19 2016-02-16 Verinata Health, Inc. Detecting and classifying copy number variation
WO2011091063A1 (en) 2010-01-19 2011-07-28 Verinata Health, Inc. Partition defined detection methods
US9323888B2 (en) 2010-01-19 2016-04-26 Verinata Health, Inc. Detecting and classifying copy number variation
US20120010085A1 (en) 2010-01-19 2012-01-12 Rava Richard P Methods for determining fraction of fetal nucleic acids in maternal samples
US20110312503A1 (en) 2010-01-23 2011-12-22 Artemis Health, Inc. Methods of fetal abnormality detection
US10351905B2 (en) 2010-02-12 2019-07-16 Bio-Rad Laboratories, Inc. Digital analyte analysis
US9399797B2 (en) 2010-02-12 2016-07-26 Raindance Technologies, Inc. Digital analyte analysis
US9366632B2 (en) 2010-02-12 2016-06-14 Raindance Technologies, Inc. Digital analyte analysis
EP3392349A1 (en) * 2010-02-12 2018-10-24 Raindance Technologies, Inc. Digital analyte analysis
US8399198B2 (en) 2010-03-02 2013-03-19 Bio-Rad Laboratories, Inc. Assays with droplets transformed into capsules
US8774488B2 (en) 2010-03-11 2014-07-08 Cellscape Corporation Method and device for identification of nucleated red blood cells from a maternal blood sample
JP2013524171A (ja) 2010-03-25 2013-06-17 クァンタライフ・インコーポレーテッド 液滴ベースのアッセイのための液滴の発生
CA2767114A1 (en) 2010-03-25 2011-09-29 Bio-Rad Laboratories, Inc. Droplet transport system for detection
CA2767113A1 (en) 2010-03-25 2011-09-29 Bio-Rad Laboratories, Inc. Detection system for droplet-based assays
CA2790416C (en) 2010-03-26 2017-05-23 Mayo Foundation For Medical Education And Research Methods and materials for detecting colorectal neoplasm
US9068017B2 (en) 2010-04-08 2015-06-30 Ibis Biosciences, Inc. Compositions and methods for inhibiting terminal transferase activity
EP2854057B1 (en) * 2010-05-18 2018-03-07 Natera, Inc. Methods for non-invasive pre-natal ploidy calling
US11332793B2 (en) 2010-05-18 2022-05-17 Natera, Inc. Methods for simultaneous amplification of target loci
US11332785B2 (en) 2010-05-18 2022-05-17 Natera, Inc. Methods for non-invasive prenatal ploidy calling
US11408031B2 (en) 2010-05-18 2022-08-09 Natera, Inc. Methods for non-invasive prenatal paternity testing
US9677118B2 (en) 2014-04-21 2017-06-13 Natera, Inc. Methods for simultaneous amplification of target loci
US10316362B2 (en) * 2010-05-18 2019-06-11 Natera, Inc. Methods for simultaneous amplification of target loci
AU2015252046B2 (en) * 2010-05-18 2017-10-19 Natera, Inc. Methods for Non-Invasive Prenatal Ploidy Calling
US11339429B2 (en) 2010-05-18 2022-05-24 Natera, Inc. Methods for non-invasive prenatal ploidy calling
US11939634B2 (en) 2010-05-18 2024-03-26 Natera, Inc. Methods for simultaneous amplification of target loci
US20190010543A1 (en) 2010-05-18 2019-01-10 Natera, Inc. Methods for simultaneous amplification of target loci
US11322224B2 (en) 2010-05-18 2022-05-03 Natera, Inc. Methods for non-invasive prenatal ploidy calling
US11326208B2 (en) 2010-05-18 2022-05-10 Natera, Inc. Methods for nested PCR amplification of cell-free DNA
US11203786B2 (en) 2010-08-06 2021-12-21 Ariosa Diagnostics, Inc. Detection of target nucleic acids using hybridization
US10167508B2 (en) 2010-08-06 2019-01-01 Ariosa Diagnostics, Inc. Detection of genetic abnormalities
US8700338B2 (en) 2011-01-25 2014-04-15 Ariosa Diagnosis, Inc. Risk calculation for evaluation of fetal aneuploidy
US11031095B2 (en) 2010-08-06 2021-06-08 Ariosa Diagnostics, Inc. Assay systems for determination of fetal copy number variation
US20120034603A1 (en) 2010-08-06 2012-02-09 Tandem Diagnostics, Inc. Ligation-based detection of genetic variants
US10533223B2 (en) 2010-08-06 2020-01-14 Ariosa Diagnostics, Inc. Detection of target nucleic acids using hybridization
US20130040375A1 (en) 2011-08-08 2013-02-14 Tandem Diagnotics, Inc. Assay systems for genetic analysis
US20130261003A1 (en) 2010-08-06 2013-10-03 Ariosa Diagnostics, In. Ligation-based detection of genetic variants
US20140342940A1 (en) 2011-01-25 2014-11-20 Ariosa Diagnostics, Inc. Detection of Target Nucleic Acids using Hybridization
EP3447155A1 (en) 2010-09-30 2019-02-27 Raindance Technologies, Inc. Sandwich assays in droplets
EP2630257B1 (en) 2010-10-22 2017-08-02 Oslo Universitetssykehus HF Methods and kits for detection of 5-hydroxymethylcytosine
EP2633311A4 (en) * 2010-10-26 2014-05-07 Univ Stanford NON-INVASIVE F TAL GENE SCREENING BY SEQUENCING ANALYSIS
DE202011110979U1 (de) 2010-11-01 2017-12-04 Bio-Rad Laboratories, Inc. System zum Bilden von Emulsionen
US8877442B2 (en) 2010-12-07 2014-11-04 The Board Of Trustees Of The Leland Stanford Junior University Non-invasive determination of fetal inheritance of parental haplotypes at the genome-wide scale
CN103608466B (zh) 2010-12-22 2020-09-18 纳特拉公司 非侵入性产前亲子鉴定方法
EP2661507B1 (en) 2011-01-05 2020-04-08 The Chinese University Of Hong Kong Noninvasive prenatal genotyping of fetal sex chromosomes
US9994897B2 (en) 2013-03-08 2018-06-12 Ariosa Diagnostics, Inc. Non-invasive fetal sex determination
US11270781B2 (en) 2011-01-25 2022-03-08 Ariosa Diagnostics, Inc. Statistical analysis for non-invasive sex chromosome aneuploidy determination
US10131947B2 (en) 2011-01-25 2018-11-20 Ariosa Diagnostics, Inc. Noninvasive detection of fetal aneuploidy in egg donor pregnancies
EP3546595B1 (en) 2011-01-25 2023-02-15 Roche Diagnostics GmbH Risk calculation for evaluation of fetal aneuploidy
US8756020B2 (en) 2011-01-25 2014-06-17 Ariosa Diagnostics, Inc. Enhanced risk probabilities using biomolecule estimations
EP2670893B1 (en) 2011-02-02 2018-06-27 Exact Sciences Development Company, LLC Digital sequence analysis of dna methylation
JP2014506465A (ja) 2011-02-09 2014-03-17 バイオ−ラド ラボラトリーズ，インコーポレイティド 核酸の分析
BR112013020220B1 (pt) 2011-02-09 2020-03-17 Natera, Inc. Método para determinar o estado de ploidia de um cromossomo em um feto em gestação
EP3760732A1 (en) 2011-02-09 2021-01-06 Natera, Inc. Methods for non-invasive prenatal ploidy calling
EP3412778A1 (en) 2011-02-11 2018-12-12 Raindance Technologies, Inc. Methods for forming mixed droplets
WO2012112804A1 (en) 2011-02-18 2012-08-23 Raindance Technoligies, Inc. Compositions and methods for molecular labeling
WO2012118745A1 (en) 2011-02-28 2012-09-07 Arnold Oliphant Assay systems for detection of aneuploidy and sex determination
JP2014508528A (ja) 2011-03-10 2014-04-10 オスロ ウニヴェルスィテーツスィーケフース ハーエフ 消化管癌の検出方法および検出マーカー
WO2012129187A1 (en) 2011-03-18 2012-09-27 Bio-Rad Laboratories, Inc. Multiplexed digital assays with combinatorial use of signals
JP5863946B2 (ja) 2011-04-12 2016-02-17 ベリナタ ヘルス インコーポレイテッド 多型カウントを用いたゲノム画分の分析
GB2484764B (en) 2011-04-14 2012-09-05 Verinata Health Inc Normalizing chromosomes for the determination and verification of common and rare chromosomal aneuploidies
US9411937B2 (en) 2011-04-15 2016-08-09 Verinata Health, Inc. Detecting and classifying copy number variation
AU2012249759A1 (en) 2011-04-25 2013-11-07 Bio-Rad Laboratories, Inc. Methods and compositions for nucleic acid analysis
CA2834218C (en) 2011-04-29 2021-02-16 Sequenom, Inc. Quantification of a minority nucleic acid species using inhibitory oligonucleotides
EP2704740B1 (en) 2011-05-04 2016-10-05 Streck, Inc. Inactivated swine flu virus and methods of preparing it
EP2707510B1 (en) 2011-05-12 2017-07-12 Exact Sciences Corporation Isolation of nucleic acids
US8993341B2 (en) 2011-05-12 2015-03-31 Exact Sciences Corporation Removal of PCR inhibitors
US8808990B2 (en) 2011-05-12 2014-08-19 Exact Sciences Corporation Serial isolation of multiple DNA targets from stool
US8841071B2 (en) 2011-06-02 2014-09-23 Raindance Technologies, Inc. Sample multiplexing
EP3709018A1 (en) 2011-06-02 2020-09-16 Bio-Rad Laboratories, Inc. Microfluidic apparatus for identifying components of a chemical reaction
WO2012177792A2 (en) 2011-06-24 2012-12-27 Sequenom, Inc. Methods and processes for non-invasive assessment of a genetic variation
AU2012261664B2 (en) 2011-06-29 2014-07-03 Bgi Genomics Co., Ltd. Noninvasive detection of fetal genetic abnormality
US8658430B2 (en) 2011-07-20 2014-02-25 Raindance Technologies, Inc. Manipulating droplet size
WO2013019714A1 (en) 2011-07-29 2013-02-07 The Trustees Of Columbia University In The City Of New York Mems affinity sensor for continuous monitoring of analytes
US8712697B2 (en) 2011-09-07 2014-04-29 Ariosa Diagnostics, Inc. Determination of copy number variations using binomial probability calculations
CN103732760A (zh) * 2011-09-23 2014-04-16 纽约市哥伦比亚大学理事会 核酸在微芯片上的分离和富集
US10196681B2 (en) 2011-10-06 2019-02-05 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US9367663B2 (en) 2011-10-06 2016-06-14 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US10424394B2 (en) 2011-10-06 2019-09-24 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
WO2013052907A2 (en) 2011-10-06 2013-04-11 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US9984198B2 (en) 2011-10-06 2018-05-29 Sequenom, Inc. Reducing sequence read count error in assessment of complex genetic variations
US8688388B2 (en) 2011-10-11 2014-04-01 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
AU2012327251A1 (en) 2011-10-27 2013-05-23 Verinata Health, Inc. Set membership testers for aligning nucleic acid samples
CA2853760A1 (en) 2011-11-04 2013-05-10 Oslo Universitetssykehus Hf Methods and biomarkers for analysis of colorectal cancer
EP3425065B1 (en) 2011-12-13 2021-04-21 Oslo Universitetssykehus HF Methods and kits for detection of methylation status
WO2013101783A2 (en) 2011-12-30 2013-07-04 Bio-Rad Laboratories, Inc. Methods and compositions for performing nucleic acid amplification reactions
WO2013101743A2 (en) 2011-12-30 2013-07-04 Abbott Molecular, Inc. Microorganism nucelic acid purification from host samples
US9822417B2 (en) 2012-01-09 2017-11-21 Oslo Universitetssykehus Hf Methods and biomarkers for analysis of colorectal cancer
WO2013104994A2 (en) 2012-01-13 2013-07-18 The University Of British Columbia Multiple arm apparatus and methods for separation of particles
AU2013209499B2 (en) 2012-01-20 2018-05-10 Sequenom, Inc. Diagnostic processes that factor experimental conditions
WO2013124738A2 (en) 2012-02-21 2013-08-29 Oslo Universitetssykehus Hf Methods and biomarkers for detection and prognosis of cervical cancer
KR101256206B1 (ko) * 2012-03-02 2013-04-19 의료법인 제일의료재단 태아의 성별 결정을 위한 분석방법 및 장치
ES2930180T3 (es) 2012-03-02 2022-12-07 Sequenom Inc Métodos para enriquecer ácido nucleico canceroso a partir de una muestra biológica
US9892230B2 (en) 2012-03-08 2018-02-13 The Chinese University Of Hong Kong Size-based analysis of fetal or tumor DNA fraction in plasma
CN104350158A (zh) 2012-03-26 2015-02-11 约翰霍普金斯大学 快速非整倍性检测
EP2834376B1 (en) 2012-04-06 2017-03-15 The Chinese University Of Hong Kong Noninvasive prenatal diagnosis of fetal trisomy by allelic ratio analysis using targeted massively parallel sequencing
EP2844773B1 (en) 2012-05-04 2017-08-16 Boreal Genomics Corp. Biomarker analysis using scodaphoresis
US20150094210A1 (en) * 2012-05-14 2015-04-02 Bgi Diagnosis Co., Ltd. Method, system and computer readable medium for determining base information in predetermined area of fetus genome
US10504613B2 (en) 2012-12-20 2019-12-10 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US9920361B2 (en) 2012-05-21 2018-03-20 Sequenom, Inc. Methods and compositions for analyzing nucleic acid
WO2013177206A2 (en) 2012-05-21 2013-11-28 Fluidigm Corporation Single-particle analysis of particle populations
US10289800B2 (en) 2012-05-21 2019-05-14 Ariosa Diagnostics, Inc. Processes for calculating phased fetal genomic sequences
US11261494B2 (en) 2012-06-21 2022-03-01 The Chinese University Of Hong Kong Method of measuring a fractional concentration of tumor DNA
US10497461B2 (en) 2012-06-22 2019-12-03 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US20140004105A1 (en) 2012-06-29 2014-01-02 Sequenom, Inc. Age-related macular degeneration diagnostics
CA2878979C (en) 2012-07-13 2021-09-14 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
US9206417B2 (en) 2012-07-19 2015-12-08 Ariosa Diagnostics, Inc. Multiplexed sequential ligation-based detection of genetic variants
CA2877493C (en) 2012-07-24 2020-08-25 Natera, Inc. Highly multiplex pcr methods and compositions
US10584381B2 (en) 2012-08-14 2020-03-10 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9701998B2 (en) 2012-12-14 2017-07-11 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10752949B2 (en) 2012-08-14 2020-08-25 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10221442B2 (en) 2012-08-14 2019-03-05 10X Genomics, Inc. Compositions and methods for sample processing
US11591637B2 (en) 2012-08-14 2023-02-28 10X Genomics, Inc. Compositions and methods for sample processing
US9388465B2 (en) 2013-02-08 2016-07-12 10X Genomics, Inc. Polynucleotide barcode generation
US9951386B2 (en) 2014-06-26 2018-04-24 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10323279B2 (en) 2012-08-14 2019-06-18 10X Genomics, Inc. Methods and systems for processing polynucleotides
CN114891871A (zh) 2012-08-14 2022-08-12 10X基因组学有限公司 微胶囊组合物及方法
US10273541B2 (en) 2012-08-14 2019-04-30 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9212392B2 (en) 2012-09-25 2015-12-15 Exact Sciences Corporation Normalization of polymerase activity
US10482994B2 (en) 2012-10-04 2019-11-19 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
EP2904534B1 (en) 2012-10-04 2021-12-15 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
EP2904116A4 (en) * 2012-10-05 2016-05-11 California Inst Of Techn METHOD AND SYSTEMS FOR MICROFLUID RECYCLING AND ANALYSIS
US9710596B2 (en) 2012-11-21 2017-07-18 Exact Sciences Corporation Methods for quantifying nucleic acid variations
US10533221B2 (en) 2012-12-14 2020-01-14 10X Genomics, Inc. Methods and systems for processing polynucleotides
EP3567116A1 (en) 2012-12-14 2019-11-13 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10643738B2 (en) 2013-01-10 2020-05-05 The Chinese University Of Hong Kong Noninvasive prenatal molecular karyotyping from maternal plasma
US20130309666A1 (en) 2013-01-25 2013-11-21 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US11060145B2 (en) 2013-03-13 2021-07-13 Sequenom, Inc. Methods and compositions for identifying presence or absence of hypermethylation or hypomethylation locus
CA2902916C (en) 2013-03-14 2018-08-28 Mayo Foundation For Medical Education And Research Detecting neoplasm
CA2901773A1 (en) 2013-03-15 2014-09-18 The Chinese University Of Hong Kong Determining fetal genomes for multiple fetus pregnancies
US9340835B2 (en) 2013-03-15 2016-05-17 Boreal Genomics Corp. Method for separating homoduplexed and heteroduplexed nucleic acids
EP2981921B1 (en) 2013-04-03 2023-01-18 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
WO2014184684A2 (en) 2013-05-16 2014-11-20 Oslo Universitetssykehus Hf Methods and biomarkers for detection of hematological cancers
WO2014190286A2 (en) 2013-05-24 2014-11-27 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
KR20240014606A (ko) 2013-06-21 2024-02-01 시쿼넘, 인코포레이티드 유전적 변이의 비침습 평가를 위한 방법 및 프로세스
US10091984B2 (en) 2013-07-24 2018-10-09 Streck, Inc. Compositions and methods for stabilizing circulating tumor cells
US20150232931A1 (en) 2013-09-20 2015-08-20 The Regents Of The University Of Michigan Compositions and methods for the analysis of radiosensitivity
US10262755B2 (en) 2014-04-21 2019-04-16 Natera, Inc. Detecting cancer mutations and aneuploidy in chromosomal segments
US10577655B2 (en) 2013-09-27 2020-03-03 Natera, Inc. Cell free DNA diagnostic testing standards
WO2015048535A1 (en) 2013-09-27 2015-04-02 Natera, Inc. Prenatal diagnostic resting standards
US11901041B2 (en) 2013-10-04 2024-02-13 Bio-Rad Laboratories, Inc. Digital analysis of nucleic acid modification
CA2925528C (en) 2013-10-04 2023-09-05 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US10438691B2 (en) 2013-10-07 2019-10-08 Sequenom, Inc. Non-invasive assessment of chromosome alterations using change in subsequence mappability
WO2015066695A1 (en) 2013-11-04 2015-05-07 Exact Sciences Corporation Multiple-control calibrators for dna quantitation
US9944977B2 (en) 2013-12-12 2018-04-17 Raindance Technologies, Inc. Distinguishing rare variations in a nucleic acid sequence from a sample
US10138524B2 (en) 2013-12-19 2018-11-27 Exact Sciences Development Company, Llc Synthetic nucleic acid control molecules
WO2015103367A1 (en) 2013-12-31 2015-07-09 Raindance Technologies, Inc. System and method for detection of rna species
WO2015107430A2 (en) 2014-01-16 2015-07-23 Oslo Universitetssykehus Hf Methods and biomarkers for detection and prognosis of cervical cancer
US11365447B2 (en) 2014-03-13 2022-06-21 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US11078539B2 (en) 2014-03-31 2021-08-03 Mayo Foundation For Medical Education And Research Detecting colorectal neoplasm
US9694361B2 (en) 2014-04-10 2017-07-04 10X Genomics, Inc. Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same
AU2015249846B2 (en) 2014-04-21 2021-07-22 Natera, Inc. Detecting mutations and ploidy in chromosomal segments
WO2015200871A1 (en) * 2014-06-26 2015-12-30 10X Genomics, Inc. Methods and compositions for sample analysis
CN113249435A (zh) 2014-06-26 2021-08-13 10X基因组学有限公司 分析来自单个细胞或细胞群体的核酸的方法
KR102441391B1 (ko) 2014-07-25 2022-09-07 유니버시티 오브 워싱톤 무세포 dna를 생성하는 조직 및/또는 세포 유형을 결정하는 방법 및 이를 사용하여 질환 또는 장애를 확인하는 방법
US11783911B2 (en) 2014-07-30 2023-10-10 Sequenom, Inc Methods and processes for non-invasive assessment of genetic variations
WO2016022696A1 (en) 2014-08-05 2016-02-11 The Trustees Of Columbia University In The City Of New York Method of isolating aptamers for minimal residual disease detection
BR112017008877A2 (pt) 2014-10-29 2018-07-03 10X Genomics Inc métodos e composições para sequenciamento de ácido nucleico-alvo
US9975122B2 (en) 2014-11-05 2018-05-22 10X Genomics, Inc. Instrument systems for integrated sample processing
EP3230476B1 (en) 2014-12-12 2020-02-05 Exact Sciences Development Company, LLC Zdhhc1 for normalizing methylation detection assays
CN107003314B (zh) 2014-12-12 2021-10-15 精密科学公司 用于进行甲基化检测测定的组合物和方法
AU2016207023B2 (en) 2015-01-12 2019-12-05 10X Genomics, Inc. Processes and systems for preparing nucleic acid sequencing libraries and libraries prepared using same
US10364467B2 (en) 2015-01-13 2019-07-30 The Chinese University Of Hong Kong Using size and number aberrations in plasma DNA for detecting cancer
CN107771221B (zh) 2015-02-10 2021-11-02 香港中文大学 用于癌症筛查和胎儿分析的突变检测
WO2016137973A1 (en) 2015-02-24 2016-09-01 10X Genomics Inc Partition processing methods and systems
CN115651972A (zh) 2015-02-24 2023-01-31 10X 基因组学有限公司 用于靶向核酸序列覆盖的方法
US11168351B2 (en) 2015-03-05 2021-11-09 Streck, Inc. Stabilization of nucleic acids in urine
CN107532124B (zh) 2015-03-27 2022-08-09 精密科学公司 检测食管疾病
US11479812B2 (en) 2015-05-11 2022-10-25 Natera, Inc. Methods and compositions for determining ploidy
WO2016185284A1 (en) 2015-05-20 2016-11-24 Boreal Genomics, Inc. Method for isolating target nucleic acid using heteroduplex binding proteins
AU2016269332B2 (en) 2015-05-22 2021-08-12 Medicover Public Co Ltd Multiplexed parallel analysis of targeted genomic regions for non-invasive prenatal testing
CN104951671B (zh) * 2015-06-10 2017-09-19 东莞博奥木华基因科技有限公司 基于单样本外周血检测胎儿染色体非整倍性的装置
US10955411B2 (en) 2015-08-04 2021-03-23 Psomagen, Inc. Manipulation of sample droplets with an electrode system
US10647981B1 (en) 2015-09-08 2020-05-12 Bio-Rad Laboratories, Inc. Nucleic acid library generation methods and compositions
KR101848438B1 (ko) 2015-10-29 2018-04-13 바이오코아 주식회사 디지털 pcr을 이용한 산전진단 방법
WO2017074094A1 (en) * 2015-10-29 2017-05-04 Biocore Co., Ltd. A method for prenatal diagnosis using digital pcr.
CN108350485A (zh) 2015-10-30 2018-07-31 精密科学发展有限责任公司 血浆dna的多重扩增检测测定以及分离和检测
US20170145475A1 (en) 2015-11-20 2017-05-25 Streck, Inc. Single spin process for blood plasma separation and plasma composition including preservative
EP3384048B1 (en) 2015-12-04 2021-03-24 10X Genomics, Inc. Methods and compositions for nucleic acid analysis
US11753682B2 (en) 2016-03-07 2023-09-12 Father Flanagan's Boys'Home Noninvasive molecular controls
WO2017180909A1 (en) 2016-04-13 2017-10-19 Nextgen Jane, Inc. Sample collection and preservation devices, systems and methods
CA3022911A1 (en) 2016-05-05 2017-11-09 Exact Sciences Development Company, Llc Detection of lung neoplasia by analysis of methylated dna
US20170321286A1 (en) 2016-05-05 2017-11-09 Exact Sciences Corporation Detection of lung neoplasia by amplification of rna sequences
WO2017197338A1 (en) 2016-05-13 2017-11-16 10X Genomics, Inc. Microfluidic systems and methods of use
CA3029842A1 (en) 2016-07-19 2018-01-25 Exact Sciences Development Company, Llc Methylated control dna
US11208680B2 (en) 2016-07-19 2021-12-28 Exact Sciences Development Company, Llc Nucleic acid control molecules from non-human organisms
CA3030890A1 (en) 2016-07-27 2018-02-01 Sequenom, Inc. Genetic copy number alteration classifications
WO2018022991A1 (en) 2016-07-29 2018-02-01 Streck, Inc. Suspension composition for hematology analysis control
CA3034903A1 (en) 2016-09-02 2018-03-08 Mayo Foundation For Medical Education And Research Detecting hepatocellular carcinoma
CA3037366A1 (en) 2016-09-29 2018-04-05 Myriad Women's Health, Inc. Noninvasive prenatal screening using dynamic iterative depth optimization
US11485996B2 (en) 2016-10-04 2022-11-01 Natera, Inc. Methods for characterizing copy number variation using proximity-litigation sequencing
AU2017347790A1 (en) 2016-10-24 2019-05-23 Grail, Inc. Methods and systems for tumor detection
US10011870B2 (en) 2016-12-07 2018-07-03 Natera, Inc. Compositions and methods for identifying nucleic acid molecules
US10815525B2 (en) 2016-12-22 2020-10-27 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10550429B2 (en) 2016-12-22 2020-02-04 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10011872B1 (en) 2016-12-22 2018-07-03 10X Genomics, Inc. Methods and systems for processing polynucleotides
WO2018127786A1 (en) 2017-01-06 2018-07-12 Oslo Universitetssykehus Hf Compositions and methods for determining a treatment course of action
CA3207879A1 (en) 2017-01-24 2018-08-02 Sequenom, Inc. Methods and processes for assessment of genetic variations
MY197535A (en) 2017-01-25 2023-06-21 Univ Hong Kong Chinese Diagnostic applications using nucleic acid fragments
CA3049459A1 (en) 2017-01-27 2018-08-02 Exact Sciences Development Company, Llc Detection of colon neoplasia by analysis of methylated dna
CN117512066A (zh) 2017-01-30 2024-02-06 10X基因组学有限公司 用于基于微滴的单细胞条形编码的方法和系统
AU2018225348A1 (en) 2017-02-21 2019-07-18 Natera, Inc. Compositions, methods, and kits for isolating nucleic acids
CN109526228B (zh) 2017-05-26 2022-11-25 10X基因组学有限公司 转座酶可接近性染色质的单细胞分析
US10400235B2 (en) 2017-05-26 2019-09-03 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
CN110914448A (zh) 2017-06-02 2020-03-24 昂飞股份有限公司 使用差异性标记的等位基因特异性探针分析混合样品的基于阵列的方法
CN108342455B (zh) * 2017-06-25 2021-11-30 北京新羿生物科技有限公司 一种从母体外周血检测胎儿非整倍体染色体的方法及其试剂盒
ES2924224T3 (es) 2017-07-07 2022-10-05 Nipd Genetics Public Company Ltd Análisis paralelo multiplexado con enriquecimiento de blancos para la evaluación de muestras de ADN fetal
PT3649259T (pt) 2017-07-07 2022-06-15 Nipd Genetics Public Company Ltd Análise paralela multiplexada enriquecida para alvo para avaliação do risco para estados genéticos
AU2018298443A1 (en) 2017-07-07 2020-01-16 Medicover Public Co Ltd Target-enriched multiplexed parallel analysis for assessment of tumor biomarkers
WO2019008148A1 (en) 2017-07-07 2019-01-10 Nipd Genetics Public Company Limited ENRICHMENT OF TARGETED GENOMIC REGIONS FOR MULTIPLEXED PARALLEL ANALYSIS
WO2019033065A1 (en) * 2017-08-11 2019-02-14 Atila Biosystems, Inc. DIGITAL AMPLIFICATION WITH LIMITED NUCLEOTIDE COMPOSITION PRIMERS
SK862017A3 (sk) 2017-08-24 2020-05-04 Grendar Marian Doc Mgr Phd Spôsob použitia fetálnej frakcie a chromozómovej reprezentácie pri určovaní aneuploidného stavu v neinvazívnom prenatálnom testovaní
WO2019084489A1 (en) 2017-10-27 2019-05-02 Juno Diagnostics, Inc. DEVICES, SYSTEMS AND METHODS FOR ULTRA-LOW VOLUMES LIQUID BIOPSY
SG11201913654QA (en) 2017-11-15 2020-01-30 10X Genomics Inc Functionalized gel beads
US10829815B2 (en) 2017-11-17 2020-11-10 10X Genomics, Inc. Methods and systems for associating physical and genetic properties of biological particles
US10648025B2 (en) 2017-12-13 2020-05-12 Exact Sciences Development Company, Llc Multiplex amplification detection assay II
KR102036609B1 (ko) * 2018-02-12 2019-10-28 바이오코아 주식회사 디지털 pcr을 이용한 산전진단 방법
WO2019169043A1 (en) * 2018-02-28 2019-09-06 ChromaCode, Inc. Molecular targets for fetal nucleic acid analysis
CN110832086A (zh) 2018-04-02 2020-02-21 伊鲁米那股份有限公司 用于制造用于基于序列的遗传检验的对照的组合物和方法
WO2019195346A1 (en) 2018-04-02 2019-10-10 Progenity, Inc. Methods, systems, and compositions for counting nucleic acid molecules
EP3775271A1 (en) 2018-04-06 2021-02-17 10X Genomics, Inc. Systems and methods for quality control in single cell processing
AU2019251504A1 (en) 2018-04-14 2020-08-13 Natera, Inc. Methods for cancer detection and monitoring by means of personalized detection of circulating tumor DNA
CN109097451A (zh) * 2018-04-23 2018-12-28 上海浦东解码生命科学研究院 一种检测g6pd缺乏症致病基因突变的试剂盒
US20210199582A1 (en) * 2018-06-28 2021-07-01 The Regents Of The University Of California Producing a composite image of a stained tissue sample by combining image data obtained through brightfield and fluorescence imaging modes
WO2020010255A1 (en) 2018-07-03 2020-01-09 Natera, Inc. Methods for detection of donor-derived cell-free dna
US11525159B2 (en) 2018-07-03 2022-12-13 Natera, Inc. Methods for detection of donor-derived cell-free DNA
CA3107467A1 (en) 2018-09-07 2020-03-12 Sequenom, Inc. Methods, and systems to detect transplant rejection
US11408030B2 (en) 2018-09-10 2022-08-09 Andy Madrid Test for detecting Alzheimer's disease
WO2020069350A1 (en) 2018-09-27 2020-04-02 Grail, Inc. Methylation markers and targeted methylation probe panel
US20220017966A1 (en) 2018-11-16 2022-01-20 Oslo Universitetssykehus Hf Methods and compositions for characterizing bladder cancer
US20220056534A1 (en) 2018-12-17 2022-02-24 Natera, Inc. Methods for analysis of circulating cells
TWI725686B (zh) 2018-12-26 2021-04-21 財團法人工業技術研究院 用於產生液珠的管狀結構及液珠產生方法
EP3927845A1 (en) 2019-02-19 2021-12-29 Sequenom, Inc. Compositions, methods, and systems to detect hematopoietic stem cell transplantation status
EP3947718A4 (en) 2019-04-02 2022-12-21 Enumera Molecular, Inc. METHODS, SYSTEMS AND COMPOSITIONS FOR COUNTING NUCLEIC ACID MOLECULES
JP2022553575A (ja) 2019-10-31 2022-12-23 マヨ ファウンデーション フォア メディカル エデュケーション アンド リサーチ 卵巣癌の検出
US11211144B2 (en) 2020-02-18 2021-12-28 Tempus Labs, Inc. Methods and systems for refining copy number variation in a liquid biopsy assay
US11211147B2 (en) 2020-02-18 2021-12-28 Tempus Labs, Inc. Estimation of circulating tumor fraction using off-target reads of targeted-panel sequencing
US11475981B2 (en) 2020-02-18 2022-10-18 Tempus Labs, Inc. Methods and systems for dynamic variant thresholding in a liquid biopsy assay
WO2021174079A2 (en) 2020-02-28 2021-09-02 Laboratory Corporation Of America Holdings Compositions, methods, and systems for paternity determination
WO2021237105A1 (en) * 2020-05-22 2021-11-25 Invitae Corporation Methods for determining a genetic variation
US20230357852A1 (en) 2020-08-19 2023-11-09 Mayo Foundation For Medical Education And Research Detecting non-hodgkin lymphoma
CA3195721A1 (en) 2020-09-21 2022-03-24 Progenity, Inc. Compositions and methods for isolation of cell-free dna
BR112023021616A2 (pt) 2021-04-22 2024-01-16 Natera Inc Métodos para determinar a velocidade de crescimento do tumor
AU2022323972A1 (en) 2021-08-02 2024-01-25 Natera, Inc. Methods for detecting neoplasm in pregnant women
WO2023021330A1 (en) 2021-08-16 2023-02-23 University Of Oslo Compositions and methods for determining a treatment course of action
CA3230790A1 (en) 2021-09-01 2023-03-09 Natera, Inc. Methods for non-invasive prenatal testing
WO2023133131A1 (en) 2022-01-04 2023-07-13 Natera, Inc. Methods for cancer detection and monitoring

Family Cites Families (83)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US994963A (en) * 1910-12-16 1911-06-13 Louis O Sutton Game apparatus.
US5641628A (en) 1989-11-13 1997-06-24 Children's Medical Center Corporation Non-invasive method for isolation and detection of fetal DNA
AU2765992A (en) * 1991-10-03 1993-05-03 Indiana University Foundation Method for screening for alzheimer's disease
US5432054A (en) 1994-01-31 1995-07-11 Applied Imaging Method for separating rare cells from a population of cells
US5695934A (en) * 1994-10-13 1997-12-09 Lynx Therapeutics, Inc. Massively parallel sequencing of sorted polynucleotides
US6100029A (en) 1996-08-14 2000-08-08 Exact Laboratories, Inc. Methods for the detection of chromosomal aberrations
GB9704444D0 (en) 1997-03-04 1997-04-23 Isis Innovation Non-invasive prenatal diagnosis
US20010051341A1 (en) 1997-03-04 2001-12-13 Isis Innovation Limited Non-invasive prenatal diagnosis
US6143496A (en) 1997-04-17 2000-11-07 Cytonix Corporation Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly
US6566101B1 (en) 1997-06-16 2003-05-20 Anthony P. Shuber Primer extension methods for detecting nucleic acids
US20030022207A1 (en) 1998-10-16 2003-01-30 Solexa, Ltd. Arrayed polynucleotides and their use in genome analysis
US6440705B1 (en) 1998-10-01 2002-08-27 Vincent P. Stanton, Jr. Method for analyzing polynucleotides
ATE556149T1 (de) 1999-02-23 2012-05-15 Caliper Life Sciences Inc Manipulation von mikropartikeln in mikrofluidischen systemen
AU3567900A (en) 1999-03-30 2000-10-16 Solexa Ltd. Polynucleotide sequencing
US6818395B1 (en) 1999-06-28 2004-11-16 California Institute Of Technology Methods and apparatus for analyzing polynucleotide sequences
US6440706B1 (en) 1999-08-02 2002-08-27 Johns Hopkins University Digital amplification
US6664056B2 (en) 2000-10-17 2003-12-16 The Chinese University Of Hong Kong Non-invasive prenatal monitoring
US20020164816A1 (en) 2001-04-06 2002-11-07 California Institute Of Technology Microfluidic sample separation device
US6960437B2 (en) 2001-04-06 2005-11-01 California Institute Of Technology Nucleic acid amplification utilizing microfluidic devices
US7118907B2 (en) * 2001-06-06 2006-10-10 Li-Cor, Inc. Single molecule detection systems and methods
US20050037388A1 (en) 2001-06-22 2005-02-17 University Of Geneva Method for detecting diseases caused by chromosomal imbalances
US6927028B2 (en) 2001-08-31 2005-08-09 Chinese University Of Hong Kong Non-invasive methods for detecting non-host DNA in a host using epigenetic differences between the host and non-host DNA
AU2002352858A1 (en) 2001-11-20 2003-06-10 Exact Sciences Corporation Automated sample preparation methods and devices
US7691333B2 (en) 2001-11-30 2010-04-06 Fluidigm Corporation Microfluidic device and methods of using same
AU2002351187A1 (en) 2001-11-30 2003-06-17 Fluidigm Corporation Microfluidic device and methods of using same
US6977162B2 (en) * 2002-03-01 2005-12-20 Ravgen, Inc. Rapid analysis of variations in a genome
US7442506B2 (en) 2002-05-08 2008-10-28 Ravgen, Inc. Methods for detection of genetic disorders
US20070178478A1 (en) 2002-05-08 2007-08-02 Dhallan Ravinder S Methods for detection of genetic disorders
US7727720B2 (en) 2002-05-08 2010-06-01 Ravgen, Inc. Methods for detection of genetic disorders
US7106905B2 (en) * 2002-08-23 2006-09-12 Hewlett-Packard Development Company, L.P. Systems and methods for processing text-based electronic documents
US7704687B2 (en) 2002-11-15 2010-04-27 The Johns Hopkins University Digital karyotyping
CA2513292C (en) 2003-01-17 2016-04-05 The Chinese University Of Hong Kong Circulating mrna as diagnostic markers for pregnancy-related disorders
AU2004217872B2 (en) 2003-03-05 2010-03-25 Genetic Technologies Limited Identification of fetal DNA and fetal cell markers in maternal plasma or serum
US20040209299A1 (en) * 2003-03-07 2004-10-21 Rubicon Genomics, Inc. In vitro DNA immortalization and whole genome amplification using libraries generated from randomly fragmented DNA
US7476363B2 (en) 2003-04-03 2009-01-13 Fluidigm Corporation Microfluidic devices and methods of using same
WO2004089810A2 (en) 2003-04-03 2004-10-21 Fluidigm Corp. Microfluidic devices and methods of using same
US20040197832A1 (en) 2003-04-03 2004-10-07 Mor Research Applications Ltd. Non-invasive prenatal genetic diagnosis using transcervical cells
US20050145496A1 (en) 2003-04-03 2005-07-07 Federico Goodsaid Thermal reaction device and method for using the same
US7604965B2 (en) 2003-04-03 2009-10-20 Fluidigm Corporation Thermal reaction device and method for using the same
EP1641809B2 (en) 2003-07-05 2018-10-03 The Johns Hopkins University Method and compositions for detection and enumeration of genetic variations
WO2005023091A2 (en) 2003-09-05 2005-03-17 The Trustees Of Boston University Method for non-invasive prenatal diagnosis
CN101985619B (zh) 2003-10-08 2014-08-20 波士顿大学信托人 染色体异常的产前诊断方法
EP1524321B2 (en) * 2003-10-16 2014-07-23 Sequenom, Inc. Non-invasive detection of fetal genetic traits
WO2005039389A2 (en) 2003-10-22 2005-05-06 454 Corporation Sequence-based karyotyping
CA2544178A1 (en) 2003-10-30 2005-05-19 Tufts-New England Medical Center Prenatal diagnosis using cell-free fetal dna in amniotic fluid
US7667001B1 (en) * 2004-01-27 2010-02-23 Compugen Ltd. Nucleotide and amino acid sequences, and assays and methods of use thereof for diagnosis of lung cancer
US20100216151A1 (en) 2004-02-27 2010-08-26 Helicos Biosciences Corporation Methods for detecting fetal nucleic acids and diagnosing fetal abnormalities
US20060046258A1 (en) 2004-02-27 2006-03-02 Lapidus Stanley N Applications of single molecule sequencing
US20100216153A1 (en) 2004-02-27 2010-08-26 Helicos Biosciences Corporation Methods for detecting fetal nucleic acids and diagnosing fetal abnormalities
CA2555259A1 (en) 2004-02-27 2005-09-09 Applera Corporation Genetic polymorphisms associated with stroke, methods of detection and uses thereof
US20050233338A1 (en) * 2004-04-20 2005-10-20 Barrett Michael T Methods and compositions for assessing chromosome copy number
US7709194B2 (en) 2004-06-04 2010-05-04 The Chinese University Of Hong Kong Marker for prenatal diagnosis and monitoring
DE102004036285A1 (de) * 2004-07-27 2006-02-16 Advalytix Ag Verfahren zum Bestimmen der Häufigkeit von Sequenzen einer Probe
EP1851543A2 (en) 2005-02-24 2007-11-07 Compugen Ltd. Novel diagnostic markers, especially for in vivo imaging, and assays and methods of use thereof
TWI367260B (en) 2005-03-18 2012-07-01 Univ Hong Kong Chinese Method for detecting the presence of a fetus with trisomy 21 in a pregnant woman and kit thereof
AU2006224971B2 (en) 2005-03-18 2009-07-02 Boston University A method for the detection of chromosomal aneuploidies
US20070196820A1 (en) 2005-04-05 2007-08-23 Ravi Kapur Devices and methods for enrichment and alteration of cells and other particles
WO2007044091A2 (en) 2005-06-02 2007-04-19 Fluidigm Corporation Analysis using microfluidic partitioning devices
WO2007001259A1 (en) 2005-06-16 2007-01-04 Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Methods and materials for identifying polymorphic variants, diagnosing susceptibilities, and treating disease
US20070059680A1 (en) 2005-09-15 2007-03-15 Ravi Kapur System for cell enrichment
ES2595373T3 (es) 2006-02-02 2016-12-29 The Board Of Trustees Of The Leland Stanford Junior University Prueba genética no invasiva mediante análisis digital
WO2007100911A2 (en) 2006-02-28 2007-09-07 University Of Louisville Research Foundation Detecting fetal chromosomal abnormalities using tandem single nucleotide polymorphisms
AU2007223102A1 (en) 2006-03-06 2007-09-13 The Trustees Of Columbia University In The City Of New York Specific amplification of fetal DNA sequences from a mixed, fetal-maternal source
WO2007112418A2 (en) 2006-03-28 2007-10-04 Baylor College Of Medicine Screening for down syndrome
US8058055B2 (en) 2006-04-07 2011-11-15 Agilent Technologies, Inc. High resolution chromosomal mapping
US7901884B2 (en) 2006-05-03 2011-03-08 The Chinese University Of Hong Kong Markers for prenatal diagnosis and monitoring
US7754428B2 (en) 2006-05-03 2010-07-13 The Chinese University Of Hong Kong Fetal methylation markers
US20080050739A1 (en) 2006-06-14 2008-02-28 Roland Stoughton Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats
US8137912B2 (en) 2006-06-14 2012-03-20 The General Hospital Corporation Methods for the diagnosis of fetal abnormalities
WO2007147074A2 (en) 2006-06-14 2007-12-21 Living Microsystems, Inc. Use of highly parallel snp genotyping for fetal diagnosis
WO2008111990A1 (en) 2006-06-14 2008-09-18 Cellpoint Diagnostics, Inc. Rare cell analysis using sample splitting and dna tags
EP2589668A1 (en) 2006-06-14 2013-05-08 Verinata Health, Inc Rare cell analysis using sample splitting and DNA tags
WO2009035447A1 (en) 2006-06-14 2009-03-19 Living Microsystems, Inc. Diagnosis of fetal abnormalities by comparative genomic hybridization analysis
CN101501251A (zh) 2006-06-16 2009-08-05 塞昆纳姆股份有限公司 扩增、检测和定量样品中核酸的方法和组合物
CN101495410B (zh) 2006-07-21 2011-12-28 昭和电工株式会社 透明复合材料
US20080113358A1 (en) 2006-07-28 2008-05-15 Ravi Kapur Selection of cells using biomarkers
CA2677517C (en) 2007-02-08 2015-11-03 Sequenom, Inc. Nucleic acid-based tests for rhd typing, gender determination and nucleic acid quantification
US20100094562A1 (en) 2007-05-04 2010-04-15 Mordechai Shohat System, Method and Device for Comprehensive Individualized Genetic Information or Genetic Counseling
EA201201551A1 (ru) 2007-07-23 2013-08-30 Те Чайниз Юниверсити Ов Гонконг Способ диагностики рака с использованием геномного секвенирования
US20090053719A1 (en) 2007-08-03 2009-02-26 The Chinese University Of Hong Kong Analysis of nucleic acids by digital pcr
EP3378951B1 (en) 2008-09-20 2020-05-13 The Board of Trustees of the Leland Stanford Junior University Noninvasive diagnosis of aneuploidy by sequencing
US20120270739A1 (en) 2010-01-19 2012-10-25 Verinata Health, Inc. Method for sample analysis of aneuploidies in maternal samples
US8756020B2 (en) 2011-01-25 2014-06-17 Ariosa Diagnostics, Inc. Enhanced risk probabilities using biomolecule estimations

Also Published As

Publication number Publication date
EP2385143B1 (en) 2016-07-13
HK1119206A1 (en) 2009-02-27
US9777329B2 (en) 2017-10-03
HUE045358T2 (hu) 2019-12-30
EP3002339B1 (en) 2019-05-08
TR201910868T4 (tr) 2019-08-21
SI1981995T1 (sl) 2013-11-29
EP3002338B1 (en) 2019-05-08
EP2423334A3 (en) 2012-04-18
US20090170113A1 (en) 2009-07-02
US7888017B2 (en) 2011-02-15
US20100256013A1 (en) 2010-10-07
US20090170114A1 (en) 2009-07-02
DK3002338T3 (da) 2019-08-05
EP2385143A3 (en) 2011-12-21
EP3002339A1 (en) 2016-04-06
HUE030215T2 (en) 2017-04-28
PL2385143T3 (pl) 2017-02-28
US10072295B2 (en) 2018-09-11
PL1981995T5 (pl) 2019-10-31
LT3002338T (lt) 2019-10-25
US9441273B2 (en) 2016-09-13
ES2429408T5 (es) 2020-01-16
DK2385143T3 (en) 2016-09-19
EP3591068A1 (en) 2020-01-08
US20230287503A1 (en) 2023-09-14
US20070202525A1 (en) 2007-08-30
WO2007092473A2 (en) 2007-08-16
CY1122112T1 (el) 2020-11-25
US20100255492A1 (en) 2010-10-07
ES2429408T3 (es) 2013-11-14
SI2385143T1 (sl) 2016-11-30
US20100124752A1 (en) 2010-05-20
EP1981995B2 (en) 2019-04-24
US20100124751A1 (en) 2010-05-20
US20180346984A1 (en) 2018-12-06
US20100255493A1 (en) 2010-10-07
EP2423334A2 (en) 2012-02-29
US11692225B2 (en) 2023-07-04
PT2385143T (pt) 2016-10-18
ES2739484T3 (es) 2020-01-31
US9777328B2 (en) 2017-10-03
DK1981995T4 (da) 2019-07-22
SI1981995T2 (sl) 2019-08-30
EP2385143A2 (en) 2011-11-09
PL1981995T3 (pl) 2014-03-31
EP1981995A4 (en) 2009-09-02
PT3002338T (pt) 2019-08-02
PL3002338T3 (pl) 2019-12-31
US8008018B2 (en) 2011-08-30
WO2007092473A3 (en) 2008-11-13
EP1981995A2 (en) 2008-10-22
CY1118095T1 (el) 2017-06-28
DK1981995T3 (da) 2013-10-14
SI3002338T1 (sl) 2019-11-29
US20150104793A1 (en) 2015-04-16
EP3002338A1 (en) 2016-04-06
EP1981995B1 (en) 2013-07-10
US8293470B2 (en) 2012-10-23
LT2385143T (lt) 2016-11-10
ES2739483T3 (es) 2020-01-31

Similar Documents

Publication Publication Date Title
ES2595373T3 (es) Prueba genética no invasiva mediante análisis digital
US9353414B2 (en) Noninvasive diagnosis of fetal aneuploidy by sequencing
ES2909841T3 (es) Nuevo protocolo para preparar bibliotecas de secuenciación
Tang et al. Characterization of mitochondrial DNA heteroplasmy using a parallel sequencing system
KR102110039B1 (ko) 비만 진단을 위한 마이크로RNA-26b 또는 마이크로RNA-4449 바이오마커 및 이의 용도
CN110484621B (zh) 一种肝癌早期预警的方法
US20150031574A1 (en) Method for classification of test body fluid sample
CN111518887A (zh) 用于检测hla-b*1502等位基因的引物组、试剂盒及方法
WO2019012543A1 (en) DNA TARGETS AS SPECIFIC TISSUE METHYLATION MARKERS
US20150024390A1 (en) Method and kit for detecting specific single nucleotide polymorphism associated with ankylosing spondylitis
US20090098056A1 (en) Alpk1 gene variants in diagnosis risk of gout
CN110564861A (zh) 人类Y染色体STR基因座和InDel位点的荧光标记复合扩增试剂盒及其应用
WO2019012542A1 (en) DETECTION OF SPECIFIC DNA FROM A FABRIC
KR20170051747A (ko) 피부 주름 발생 민감도 진단용 단일염기다형성 마커 및 이의 용도
US20150292012A1 (en) Biomarkers for nod2 and/or rip2 activity related application
US20100255468A1 (en) Method of assessing gene examination data, program therefor and apparatus of the same
US9139881B2 (en) Method for assessing breast cancer susceptibility
Lin et al. Next generation sequencing as a new detection strategy for maternal cell contamination in clinical prenatal samples
Graham Sex determination
JP2020534817A (ja) 短い核酸の多重検出
KR102409336B1 (ko) 면역글로불린 a 신병증 및 혈관염 진단용 snp 마커 및 이를 이용한 진단 방법
KR102110038B1 (ko) 비만 진단을 위한 마이크로RNA let-7a 또는 let-7f 바이오마커 및 이의 용도
EP2840147A1 (en) Method for assessing endometrial cancer susceptibility
CN105886600A (zh) 一种用于FTO基因分型的ARMS-qPCR检测试剂盒及检测方法
Khalaf et al. Role of micro RNA-21 in Egyptian patients with ischemic heart disease